The 1st International Drug Discovery Workshop

The 1st International workshop on Drug discovery 2016 Book of Abstracts
The 1st International workshop on Drug

Discovery, National Research Centre
December 5-6,2016
Under the Theme of
Drug Discovery workshop

Under the patronage of
Prof.Ashraf Shaalan
President ,National Research Centre
Workshop Chairman
Prof .Asmaa Magd El-Din
Professor of Organic Chemistry, Natural
and Microbial Product Department
Workshop Cochairman
Ahmed El-Rashedy
Research Assistant, Natural and Microbial
Product Department
Abstracts Book
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General Information
Date : Dec 5-6 (2016)
Venue : National Research Centre
Conference Halls:
*New Hall
* Restaurant Hall
Registration:
At registration desk from 9-10 am on Monday 5th December in the
New Hall throughout the workshop .
Language:
Scientific activity will be in English
Slides &Date show:
Please submit your slides or CD to the slide delivery room
(Restaurant Hall) at least one hour before the presentation time .
Posters:
The poster should be placed in Restaurant Hall on December 5,6
(2016)
Website : http://drug-discovery.m-abdelhay.com/
Website Developer: Mohammed Abd Elhay
Organizing officer
Dr Noha Alsaghir Mousa Dr :Hanaa Roaiah
Dr : Fatma Abd AL Aleem Dr Weam Salah Goda
Dr Ayman Sweed Dr Huda Refat
4
Drug Discovery Workshop

08.30-10.00 a.m. Registration
10.00-10.30 a.m. Opening
10.30-11.00a.m Prof. Dr. Feras Alalia

Betting on Natural Products: Associate Dean, Research
Cytotoxic Homoisoflavones Affairs and Graduate Studies
from the Bulbs of Bellevalia Professor, Natural Products
eigii Chemistry and Analysis
College of Pharmacy
Qatar University
11.00-11.30a.m.
Development of Drug Target Prof. Dr. Naidu Subbarao

and Chemical Databases for
designing antimalarial and School of Computational and
antituberculosis agents Integrative Sciences Jawaharlal
Nehru University, New Delhi,
India
11.30-12.00a.m. Lipase-Catalyzed Kinetic Prof. Dr. Hassan Aboul-

Resolution of Racemates: A Enein
Versatile Method in Chiral
Separation and Drug Pharmaceutical and Medicinal
Development Chemistry Department,
Pharmaceutical and Drug
Industries research Division,
National Research Centre
12.00-12.30p.m. Rational Design Of Small Prof. Dr. Khaled H. S.

Molecule Immune Barakat
Checkpoints' Inhibitors :
The PD-1 Challenge Faculty of Pharmacy &
Pharmaceutical Sciences 02-
20G Katz Group-Rexall
Centre for Health Research
University of Alberta,
Edmonton, Alberta, Canada
12.30-01.00p.m. Coffee Break
01.00-01.30 p.m. Biopolymer for industrial, Prof. Dr. Mahmoud Ahmed

medical and drug delivery
5
systems Abd Elghafar
Polymers and pigments

Department, National Research
Centre
01.30-02.00a.m. Towards A Comprehensive Prof. Dr. Ameen Farouk

Fahmy
Approach To Metrics For
Green Pharmaceutical Professor Of Organic
Industry "A Unified Metrics Chemistry, Faculty of Science,
Toolkit" Ain Shams University, Cairo,
Egypt
2.00-`02.30p.m. Computer-aided drug Dr. Mahmoud Ibrahim

discovery of LTB4 inhibitors
towards treatment of Head of CompChem Lab,
inflammatory diseases Chemistry Department,
Faculty of Science, Minia
University, Minia 61519,
Egypt.
02.30-03.00 p.m. A Journey in Design, Prof. Dr. Ibrahim Tantawy

Synthesis and Development
of Novel Anticancer and President of Japan Society for
Antimalarial Agents the promotion of Science
Alumni Association in Egypt
(JSPSAAE), Professor of
Organic & Medicinal
Chemistry, El-Menoufia
University, Faculty of Science,
Chemistry Department, Shebin
El koom, Egypt
03.00-03.30 p.m. New Therapeutic and Drug Prof.Dr. Hamdy Abdelkader

Delivery Methods for the
Anterior Segment of the Eye Pharmaceutics Department,
: from bench to clinic. Faculty of Pharmacy, Minia
University
03.30-04.30p.m Lunch Break & Poster
Second Day
6
09.00-10.00 a.m. Registration
10.00-10.30a.m. Scientific Computing for Prof. Dr. Ahmed Farouk

Drug Discovery
Head of Bioinformatics unit
Head of Expert System

Development Department
CLAES ARC
10.30-11.00a.m. Active site hydration, Prof. Dr. Khaled M. Elokely

thermodynamics and drug
design Department of Pharmaceutical
Chemistry, Tanta University
11.00-11.30a.m. Synthesis and Medicinal Prof. Dr. Somaia elkarim

Significance of Novel
Heterocyclic Compounds Therapeutical Chemistry
Containing Pyrazole Moiety Department, National Research
Center
11.30-12.00p.m. Application of heterocyclic Prof. Dr. Maher A. El

compounds in the field of Hashash (D.Sc.)
chemotherapy
Professor of organic chemistry,
chemistry department, faculty
of science, Ain Shams
university
12.00-12.30 p.m. Site Identification by Ligand Prof. Dr. Atef A Abdel-Hafez

Competitive Saturation
(SILCS) in Drug Discovery Professor and Head of
Medicinal Chemistry
Department, Faculty of
Pharmacy, Assiut University,
Assiut,, Egypt
01.00-01.30p.m. Coffee Break
01.00-01.20 pm Protein Engineering an Prof. Mohamed Abd elnabi

Effective Strategy to Improve
Catalytic, Kinetic, and Department of Natural and
Thermodynamic, Properties Microbial Product, Research
of Industrial Enzymes Division of Pharmaceutical and
Drug Industries, National
Research Centre
7
01.20-01.40 pm Production and Dr. Donia H Sheir

characterization of
antimicrobial compound Department of Natural and
produced by Streptomyces Microbial Product, Research
atrovirens H33 Division of Pharmaceutical and
Research Centre
01.40-02.00 pm Advanced Microbiol tools Dr Bahgat Ezzat

for drug discovery
Department of Natural and
Microbial Product, Research
Division of Pharmaceutical and
Research Centre,
02.00-2.20 pm Penicillin G Acylase in Dr Marwa Wahba

Drugs' Industry
Research Centre
02.20-02.40pm Drug Discovery and Dr Ahmed El Rashedy

Development
Research Centre,
3.30-04.00p.m. Closing
Kindly shut off your mobiles during the session.
Monday 05.12.2016
8
Oral sessions
Main Hall (10.30-12.30pm)
Chair Persons
Prof. Dr. . Ameen Farouk Fahmy
Prof. Dr. Mahmoud Ahmed Abd Elghafar
Prof. Dr. Khaled M. Elokely
10.30-11.00a.m. Betting on Natural Products: Cytotoxic Homoisoflavones

from the Bulbs of Bellevalia eigii
Prof. Dr. Feras Alalia
Associate Dean, Research Affairs and Graduate Studies
Professor, Natural Products Chemistry and Analysis
College of Pharmacy , Qatar University
11.00-11.30a.m. Development of Drug Target and Chemical Databases for
designing antimalarial and antituberculosis agents
Prof. Dr. Naidu Subbarao
School of Computational and Integrative Sciences
Jawaharlal Nehru University, New Delhi, India
11.30-12.00P.m Lipase-Catalyzed Kinetic Resolution of Racemates: A
Versatile Method in Chiral Separation and Drug
Development
Prof. Dr. Hassan Aboul-Enein
Pharmaceutical and Medicinal Chemistry Department,
Pharmaceutical and Drug Industries research Division,
National Research Centre
12.00-12.30p.m. Rational Design Of Small Molecule Immune

Checkpoints' Inhibitors : The PD-1 Challenge
Prof. Dr. Khaled H. S. Barakat
Faculty of Pharmacy & Pharmaceutical Sciences 02-20G
Katz Group-Rexall Centre for Health Research University
of Alberta, Edmonton, Alberta, Canada
Chair Persons
9
New Hall (01.00-03.30pm)[II]

Prof. Dr. Feras Alalia
Prof. Dr. Hassan Aboul-Enein
Prof. Dr. Naidu Subbarao
01.00-01.30 p.m Biopolymer for industrial, medical and drug delivery

systems
Prof. Dr. Mahmoud Ahmed Abd Elghafar
Polymers and pigments Department, National Research
Centre
Towards A Comprehensive Approach To Metrics For
Green Pharmaceutical Industry "A Unified Metrics
01.30-02.00p.m. Toolkit
Prof. Dr. Ameen Farouk Mohamed Fahmy
Faculty of Science, Ain Shams University, Egypt
02.00-`02.30p.m. Computer-aided drug discovery of LTB4 inhibitors

towards treatment of inflammatory diseases
Dr. Mahmoud A. A. Ibrahim
Head of CompChem Lab, Chemistry Department, Faculty of

Science, Minia University, Minia
02.30-3.00 p.m. A Journey in Design, Synthesis and Development of

Novel Anticancer and Antimalarial Agents
Prof. Dr. Ibrahim Tantawy
President of Japan Society for the promotion of Science
Alumni Association in Egypt (JSPSAAE), Professor of
Organic & Medicinal Chemistry, El-Menoufia University,
Faculty of Science, Chemistry Department, Shebin El koom,
3.00-3.30 p.m. New Therapeutic and Drug Delivery Methods for the
Anterior Segment of the Eye : from bench to clinic
Prof.Dr. Hamdy Abdelkader
Pharmaceutics Department, Faculty of Pharmacy, Minia
University,Egypt
Tuesday 06.12.2016
10
Oral sessions
New Hall (10.00-12.30pm)[III]
Chair Persons
Prof .Dr : Asmaa Magdi Eldien
Prof .Dr : Amira Said
10.00-10.30a.m Scientific Computing for Drug Discovery

Prof. Dr. Ahmed Farouk
Head of Bioinformatics unit ,Head of Expert System Development
Department ,CLAES ARC
10.30-11.00am Active site hydration, thermodynamics and drug design
Prof. Dr. Khaled M. Elokely
Department of Pharmaceutical Chemistry, Tanta University
11.00-11.30am Synthesis and Medicinal Significance of Novel Heterocyclic
Compounds Containing Pyrazole Moiety
Prof. Dr. Somaia elkarim
Therapeutical Chemistry Department, National Research Center
11.30-12.00am Application of heterocyclic compounds in the field of
chemotherapy
Prof. Dr. Maher A. El Hashash(D.Sc.)
Professor of organic chemistry, chemistry department, faculty of
science, Ain Shams university
12.00-12.30 p.m. Site Identification by Ligand Competitive Saturation (SILCS) in
Drug Discovery
Prof. Dr. Atef A Abdel-Hafez
Professor and Head of Medicinal Chemistry Department, Faculty of
Pharmacy, Assiut University, Assiut,, Egypt
11
Oral sessions
New Hall (12.30-03.00pm)[IV]
Pof .Dr : Mona Shafy
Prof.Dr: Heba Elrefay
12.30-1.00 pm Protein Engineering an Effective Strategy to Improve Catalytic,
Kinetic, and Thermodynamic, Properties of Industrial Enzymes
Mohamed A. Abdel Naby
Department of Chemistry of Natural and Microbial Products ,
National Research Center, Cairo, Egypt.
01.00-01.30 pm Production and characterization of antimicrobial compound
produced by Streptomyces atrovirens H33
Dr. Donia Sheir
Department of Natural and Microbial Product, Research Division
of Pharmaceutical and Drug Industries, National Research Centre,
Dokki, Cairo, Egypt
01.30-02.00pm Advanced Microbiol tools for drug discovery
Dr Bahgat Ezzat
Dokki, Cairo, Egypt
02.00-02.30pm Penicillin G Acylase in Drugs' Industry
Dr Marwa Wahba
Dokki, Cairo, Egypt
02.30-03.00pm Drug Discovery and Development
Dr Ahmed El Rashedy
Dokki, Cairo, Egypt
Poster sessions
12
Prof. Dr. Khaled H. S. Barakat
Prof. Dr. Ibrahim Tantawy
Dr. Mahmoud Ibrahim
P: 1
Constructing white light emitting metal-organic frameworks by post-synthetic

modification
Reda M. Abdelhameed
Researcher Applied Organic Chemistry Department, National Research Centre
P:2
pH-controlled Release System for Curcumin based on Functionalized Dendritic

Mesoporous Silica Nanoparticles
Khaled EA AbouAitah , Farghali AA , Anna Swiderska-Sroda , Witold Lojkowski , Abdel-

Fattah M Razin and Khedr MH
Department of Medicinal and Aromatic Plants Research, Pharmaceutical and Drug

Industries Research Division, National Research Centre (NRC), Dokki, Giza, Egypt.
P-3
New Potent SARS-CoV 3C-Like Protease Inhibitors Derived from Thieno[2,3-d]-

pyrimidine Derivatives.
Abd El-All AS, Atta SM, Roaiah HM, Awad EM, Abdalla MM.
Department of Natural and Microbial Products, Research Division of Pharmaceutical

and Drug Industries, National Research Centre, Dokki, Giza, Egypt.
P-4
Mesoporous Silica Materials in Drug Delivery System: pH/Glutathione- Responsive

Release of Poorly Water-Soluble Pro-drug Quercetin from Two and Three-
dimensional Pore-Structure Nanoparticles
AbouAitah KEA , Farghali AA , Swiderska-Sroda A, Lojkowski W , Razin AM and Khedr

MH.
Department of Medicinal and Aromatic Plants Research, Pharmaceutical and Drug

Industries Research Division, National Research Centre (NRC), Dokki, Giza, Egypt
P: 5
13
Synthesis, biological evaluation and molecular modeling study of some

Thiadiazolodiazepine analogues as a new class of neuromuscular blocking agents
Hussein I. El-Subbagh, Adel S. El-Azab, Ghada . Hassan, Shahenda M. El-Messery,

Alaa A.-M. Abdel-Aziz,, Kamal E.H. El-Taher
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura

University, Mansoura 35516, Egypt
P :6
RAT BONE MARROW MESENCHYMAL STEM CELLS DIFFERENTIATION INTO

GERM CELLS IN VITRO
El- Husseny, A. Bossila ; Bahgat, A. El-Fiky ; yousry, A.Dowidar; Aly, M. El Refy
And Hussein, S. Hussein
Biotechnology Department, Faculty of Agriculture-Al-Azhar University-Cairo-Egypt
P:7
Bone Marrow Mesenchymal Stem Cells Restore Male Infertility in Azoospermic

Mice
Wrshana, T.A. , El-Fiky, B.A. , Dwidar Y. A. and El-Rify A.M.
Biotechnology Department, Faculty of Agriculture, University of Al-Azhar, Cairo. Egypt.
P: 8
Recovery of Female Infertility by Bone Marrow Mesenchymal Stem Cells in Rats
M Elbehary , El-Fiky, B.A. , Y. A. dwadar , A.M. El-rify.
P: 9
Synthesis, Docking Study, and Cytotoxic Evaluation of Novel Thiopyrimidines and

Their Condensed Sulfonamide Analogs
Mohamed F El-Shehry
Department of Pesticide Chemistry, National Research Centre, Dokki, Egypt
P: 10
14
Synthesis and antimicrobial activity of some potent substituted thioxothiazolidin

4-ones
Amira Said Abd-el-all

and Drug Industries, National Research Centre, Dokki, Giza, Egypt
P: 11
Synthesis of New oxazine and oxazocine derivatives and Evaluation of their

Antiproliferative Potency against Different Cancer Cell Lines
Nagwa M. Fawzy
Chemistry of Natural and Microbial Products Department, National Research Centre, 33

El Beehouth St., Dokki, Giza, Egypt.
P : 12
A Novel Multi-Component Reaction of Indoles and Formyl Furochromone was

Described for the Synthesis of Indoles Derivatives with Expected Antitumor
Activity
I.F.Zaeid , A. M. Nasef, N.M. Fawzy , A. M. Soliman M.M.E-Baroudy

P:13
Synthesis of Novel Acetamide Derivatives and Evaluation of their Antiproliferative

Potency against Different Cancer Cell Lines
Hanaa M. Roaiah , Khadiga M. Ahmed , Nagwa M. Fawzy , Joanna Wietrzy , Agata

Pawlik , Mamdouh M. Ali, Abdel Mohsen Soliman

P : 14
Efficient Synthesis of 9-substituted acridine derivatives as potential anticancer

candidates
Yasser M. Shaker

P:15
15
Design of new opioid modulators using structure- and ligand-based virtual

screening
Manal A. Nael , Vedanjali Gogineni and Khaled M. Elokely
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University,

Tanta 31527, Egypt
P : 16
Synthesis, Anticancer Activity and Molecular Docking Study of Novel 1, 3-

Diheterocycles IndoleDerivatives
Eslam R El-Sawy, Heba M Abo-Salem, Khalied Mahmoud, Eman S Zarie, Amira M El-
Metwally, Adel H Mandour
Chemistry Department of Natural Compounds, National Research Centre, Egypt
P : 17
Biosynthesis, Anticancer Screening and Molecular Docking Studies of Novel Anti-

tubulin Fungal Metabolites
Iman A. Y. Ghannama, Hanaa M. Roaiah , Adel S. Girgisb, Mamdouh M. Ali , Mona M.

Hanna, Sally S. El-Nakkady, Russell J. Coxe,
Chemistry of Natural and Microbial Products Department, National Research Centre,

Dokki, Cairo, Egypt
P:19
Anticancer Catechol-Benzothiazole Conjugates; Design, Laccase-Catalyzed Green

Synthesis and Cytotoxic Evaluation against MCF-7 Cell Line
Heba T. Abdel-Mohsen and Uwe Beifuss
Natural and Microbial Products Department, Pharmaceutical Industries Research

division, National Research Centre, Cairo, Egypt
P :20
SYNTHESIS AND ANTICANCER EVALUATION OF NOVEL 2,2,6,6-TETRAMETHYL-4-PIPERIDONE

DERIVATIVES
Mahmoud N. M. Yousif , N. M. Yousif , Hanem M. Awad
Photochemistry Department, National Research Centre, Egypt
16
17
Betting on Natural Products: Cytotoxic Homoisoflavones from the

Bulbs of Bellevalia eigii
Feras Alali a,c, Tamam El-Elimatb,c, Hanan Albatainehc, Qosay Al-Balasc, Mohammad
Ghariebehc, Wei-Lun Chenb, Steven M. Swansond, Joseph Falkinhame, Ali Eidf and Nicholas H.
Oberliesb
a Faculty of Pharmacy, Qatar University, Doha 2713,
b Department of Chemistry and Biochemistry, University of North Carolina at Greensboro,

Greensboro, NC 27402, United States
c Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan
d Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of

Illinois at Chicago, Chicago, IL 60612, United States
e Department of Biological Sciences, Virginia Polytechnic Institute and State University,

Blacksburg, VA 24061, United States
f Department of Biological and Environmental Sciences, Qatar University, Doha 2713
Eighteen compounds, 8 new and 12 known, were isolated from an organic extract of the bulbs of
Bellevalia eigii as part of a search for anticancer leads from plants. Of these, sixteen were a series
of homoisoflavonoid analogues (1-16), of which seven were new [E-bellegiin (2), 5-hydroxy-7,8-
dimethoxychroman-4-one (3), 3'-hydroxy-3,9-dihydrobellegiin (5), 6-hydroxy-3,9-
dihydrobellegiin (8), 3'-hydroxy-E-bellegiin (13), 3-hydroxy-8-demethoxy-3,9-dihydrobellegiin
(14), and 3'-hydroxy-4'-methoxy-3,9-dihydrobellegiin (15)], and two were a known phenolic
amide analogue (17) and a new methylthio acrylate derivative [bellegimycin (18)]. The structures
were elucidated using a set of spectroscopic and spectrometric techniques; the absolute
ECD
spectroscopy, while a modified Moshers ester method was used for compound 18. Optical
rotation for the known compounds 1, 4 and 11 were reported for the first time. The cytotoxic
-MB-435 (melanoma) and HT-29
(colon) cancer cell lines. Compounds 6 and 15 were the most potent on the latter cell line with
IC50 values of 1.0 and 1.1 M, respectively. When tested against a panel of bacteria and fungi,
compounds 6 and 12 showed promising activity against the Gram-positive bacterium
Mycobacterium smegmatis with MIC values of 17 and 24 g/mL, respectively. Compound 2
showed promising inhibitory anti-metastatic activity in wound-healing migration, invasion, and
adhesion tests
18
Development of Drug Target and Chemical Databases for designing

antimalarial and antituberculosis agents
Naidu Subbarao
School of Computational and Integrative Sciences Jawaharlal Nehru University, New Delhi, India
Infectious diseases have represented a global concern throughout centuries of human history,
claiming for millions of lives every year. Approximately one third of the worlds population (2
billion) is infected with Mycobacterium tuberculosis (Mtb). HIV infection has contributed to a
significant increase in the worldwide incidence of Tuberculosis. According to WHO estimates
(early 1992) over 4 million persons worldwide have been infected with HIV and Tuberculosis;
95% of them are in the developing countries. Only 5-10% of those infected will develop active
TB (not including those with HIV, for them the rate is much higher) that still translates to 8
million people becoming sick and 2 million deaths (including those with HIV) each year.
Tuberculosis will infect an estimated one billion people by 2020, killing 70 million people
worldwide. Human malaria is caused by Plasmodium falciparum is responsible for the vast
majority of the 300500 million episodes of malaria worldwide and accounts for 0.72.7 million
annual deaths. Although current treatment can be effective for tuberculosis if administered
correctly, existing drugs must be taken for at least six months to prevent relapsing disease. Low
treatment compliance contributes directly to the emergence of multidrug, extensively drug
resistant, total drug-resistant (MDR,XDR and TDR) strains of Mycobacterium tuberculosis,
which further limit the efficacy of standard therapy. The serious problem of malaria parasite drug
resistance to currently used antimalarials has led to an urgent need to develop new and effective
antimalarial molecules. There are 10 main groups of antimalarial drugs in use. Most of these
drugs are primarily active against the blood forms of the parasite. Prior to the Second World War,
Quinine, Primaquine, ChloroQuine and Mepacrine were developed. These were followed by
Proguanil and AtovaQuone (in the 1940s), Primaquine and Pyrimethamine (1950s),
Sulphadoxine/Pyrimethamine (1960s), Artemisinin (1970s,) and then a spurt of drugs in the
1980s: MefloQuine, Halofantrine and various Chinese compounds - Pyronaridine, Piperaquine,
Artemisinin derivatives-Artemether, Artesunate and Dihydroartemisinin We have developed
two Drug Target Databases listing all the known and predicted drug targets and inhibitors for
Mycobacterium tuberculosis and Plasmodium falciparum along with PfchemDB. The databases
provide a comprehensive information about each drug target regarding sequence, structural,
functional, stage specific gene expression, metabolic pathway, mechanism of action, their
inhibitors along with literature. The Drug Target Databases of Mycobacterium tuberculosis and
Plasmodium falciparum contain 122 and 90 Drug Targets (Validated and Putative) respectively.
These Drug Target Databases will become a useful resource for Drug Designing. Approximately
46 and 30 Protein drug target structures are available in PDB, for another 30 drug targets each in
Mycobacterium tuberculosis and Plasmodium falciparum, we have modeled the protein
structures, identified and validated binding sites for carrying out Structure based drug designing.
19
Drug Target identification, selection, validation and prioritization is of great importance to

develop inexpensive and effective novel inhibitors that over come the drug resistance with no
side effects of existing antituberculosis and antimalarial therapy. We have designed novel
inhibitors(hits) for prioritized drug targets DNA gyase B and DNA Polymerase III alpha subunit
of Mycobacterium tuberculosis, PfHDAC1, PfGCN5 PfPk5, pDNA gyrase B and Sir2A(Silence
information regulator with histone deacetylase activity) of Plasmodium falciparum by virtual
screening using GOLD and GLIDE docking programs.
20
Lipase-Catalyzed Kinetic Resolution of Racemates: A Versatile Method

in Chiral Separation and Drug Development
Hassan Y. Aboul-Enein
Pharmaceutical and Medicinal Chemistry Department, Pharmaceutical and Drug Industries

research Division, National Research Centre:
Enzymes and especially lipases are biological catalysts of extraordinary selectivity and efficiency.
They catalyze and regulate reactions of important biochemical pathways. In common with all
catalysts, they accelerate the attainment of chemical equilibrium but can not mediate a
thermodynamically unfavorable reaction. Since they are chiral, they are able to assert a dramatic
chiral influence on the reaction due to the chiral active site they owe. The reactant molecules are
bound instantaneously to the active site while the reaction takes place. Only one enantiomer of a
chiral reactant fits it properly and is able to undergo the reaction while the second enantiomer is
left unreacted and in enantiomerically pure form. Lipases, have been widely used in three main
types of reactions yielding optically pure compounds. These are kinetic resolution of racemic
carboxylic acids or alcohols, enantioselective group differentiations of meso dicarboxylic acids or
meso diols and enantiotopic group differentiation of prochiral dicarboxylic acid and diol
derivatives. Enantiomerically pure drugs especially those containing a secondary hydroxyl or
carboxylic functional groups are preferably synthesized by enzymatic kinetic resolution of the
racemates. This biochemical transformation process has become a standard reaction protocol to
access to enantiomarically pure compounds.1 The ways in which efficiency and practicality of
this procedure are defined is depending on a large numbers of factors. Among these factors are
scale,2 reagent costs, time allotted and required,3 suitable equipments and reliable methods used
in the determination of the enantiomeric excess of substrate and the resulting product. In this
presentation, the applications of lipases to access to enantiomarically pure compounds together
with the reliable methods used in chiral separation are discussed.
21
Rational Design Of Small Molecule Immune Checkpoints' Inhibitors:

The PD-1 Challenge
Khaled H. S. Barakat
Faculty of Pharmacy & Pharmaceutical Sciences 02-20G Katz Group-Rexall Centre for Health
Research University of Alberta, Edmonton, Alberta, Canada
Blocking the PD-1/PD-L1 pathway recently emerged as a game changer in cancer

immunotherapy, leading to the selection of monoclonal-antibodies (MABs) targeting PD-1 as
drug of the year for 2013. Although these antibodies restored exhausted T cells function to
recognize and kill tumor cells, these MABs have numerous disadvantages. These include their
very high cost and very severe side effects. Our team has been focused on designing small
molecule inhibitors for this pathway. Compared to available MAB therapies, our small molecules
may offer a more affordable, more easily administered and better controlled treatment for a
variety of cancers. Here, we demonstrate our efforts toward this goal and summarize preliminary
data on one of our promising compounds, a small molecule inhibitor for the PD-1/PD-L1
pathway that binds to PD-1 and restores the polyfunctionality of exhausted T cells.
22
Biopolymer for industrial, medical and drug delivery systems
Mahmoud Ahmed Abd El-Ghaffar
Biopolymers the eco-friendly biodegradable materials from synthesis to Applications
Polymers and Pigments Department, National Research Centre, Dokki, Cairo, Egypt
This talk will focus on the new trends and recent applications of biopolymers in industrial , drug
delivery and medical applications.
Natural polymers e.g. cellulosic materials, chitin, chitosan, starch, sodium alginate, pectine, poly
lactic acid and copolymers of lactic and glycolic acids, in addition to grafting of synthetic
monomers onto natural polymers found wide applications in enzyme immobilization1-4, drug
carriers for control release in drug delivery systems5,6, antibody immobilization7,8, and
biosensors9.
It is well known that enzymes are being used in numerous new applications in food, paper ,
leather and textiles industries resulting in cost reduction. At the same time, rapid technologies
developments are now simulating the chemistry and pharmaceutical industries to embrace
enzyme technology for health, energy, electronics and environment.
The talk will throw light on our potential in this area including the following topics:
1. Chitosan and its amino acids condensation adducts as reactive polymer supports for
cellulase and a amylase.
2. pH sensitive sodium alginate hydrogels for riboflavin controlled release .
3. Polylactic acid and polylactic-co-glycolic acid microcapsules for sustained release of

riboflavin.
4. Antibody immobilization for removal of virus C Hepatitus.
5. High Performance Formula Of Carbamazepine Extend Release.
23
Towards A Comprehensive Approach To Metrics For Green

Pharmaceutical Industry "A Unified Metrics Toolkit
Fahmy, A.F.M.
Green Pharmaceutical Industry Chemistry Department, Faculty of Science, in Shams University,

Cairo, Egypt
Email: afmfahmy42@gmail.com
Determining whether the new reactions and methodologies developed are superior to the existing
chemistries from an environmental point of view requires extensive assessment of metrics. Key
parameters covered by the unified metrics toolkit. The Metrics Toolkit allows monitoring,
measure, compare and evaluating new methodologies in terms of their green credential. The
Toolkit was split into a number of passes/levels with increasing complexity as the synthetic
reaction moves from discovery, through scale-up, towards commercialization. Yield Economy
[YE], Atom Economy [AE], Reaction Mass Efficiency [RME], Optimum Efficacy [OE], Mass
Intensity [MI] &Process Mass Intensity [PMI] are among metrics used. Another metrics allow
monitoring, solvents, health and safety, energy, catalysts. availability and applicability.
Using new greener synthetic reactions have to be economically viable. Therefore any solvent,
reagents, enzymes and catalysts should be commercially available. Applicability is a criteria
refers to how widely applicable new reactions & methodologies within the pharmaceutical
industry .The ideal synthetic strategies are step efficient[SE], with high yield economy[YE], ,
high atom economy [ AE]. Simple & safe, energy saving, economical in time & waste.
Environmentally acceptable.
1) http://www.chem21.eu.
2) Towards a holistic approach to metrics for the 21st century pharmaceutical industry.(2015).
C.Robert McElroy , Andri Constantinou , Leonie C. Jones , Louise Summerton and James H.
Clark., Green Chem., 2015, 17, 3111-3121
3) Multicomponent synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones (azlactones) using a

mechanochemical approach ;A.F. M. Fahmy, M. M. Hemdan, A. A. El-Sayed (2016)
24
Computer-aided drug discovery of LTB4 inhibitors towards treatment

of inflammatory diseases
Mahmoud A. A. Ibrahim
Head of CompChem Lab, Chemistry Department, Faculty of Science, Minia University, Minia
61519, Egypt.
Leukotriene B4 (LTB4) is a dihydroxy fatty acid derived from the 5-lipoxygenase pathway of
arachidonic acid metabolism and is an important mediator of the inflammatory process[1]. The
inhibition of LTB4 binding to G-protein-coupled receptors namely BLT1 and BLT2 is the
premise of a treatment for several inflammatory diseases[2]. Targeting these two receptors might
offer an attractive treatment option for inflammatory diseases[3]. The crystal structures of BLT1
and BLT2 receptors have not elucidated yet[4]. In the current work, homology models of BLT1
and BLT2 receptors were constructed using in-silico techniques. The BLT1 model was first built
based on a selected NMR structure with a high amino acid sequence similarity (PDB code:
2KS9). Thereafter, BLT2 model was generated based on the proposed BLT1 structure. The BLT1
and BLT2 models were then refined using molecular dynamic (MD) annealing technique. The
binding sites of the studied receptors were mapped and evaluated using docking techniques.
Based on the refined models, structure based-virtual screening of approximately 21 million drug
like molecules was performed using Autodock4.2 software. The top potent 250,000 BLT1/BLT2-
drug like molecules were future examined using advanced docking techniques. Compared to the
calculated binding energy of LTB4 complexed to BLT1 and BLT2, the more efficient drug-like
molecules were elected. Finally, a short-list of the top potent 1,000 molecules were subjected to
molecular minimization in complexation to BLT1 and BLT2 receptors, followed by binding
energy calculation using MM-GBSA approach. According to our data, potent inhibitors were
discovered for BLT1 and BLT2 with a binding score of nearly twice the value of the best pre-
identified BLT1/BLT2 antagonists. According to our results, three identified drugs (code:
CC025145, CC085892 and CC549498) would be proposed as potent anti-inflammatory
inhibitors.
References:
[1] P. Montuschi, Pharmaceuticals 2010, 3, 1792-1811.
[2] J. R. A. Goodnow, A. Hicks, A. Sidduri and A. Kowalczyk, J. Med. Chem 2010, 53, 3502-
3516.
[3] A. Hillisch, L. F. Pineda and R. Hilgenfeld, Drug Discovery Today 2004, 9, 659-669.
[4] R. E. Stenkamp, D. C. Teller and K. Palczewski., ChemBioChem 2002, 3, 963-967.
25
A Journey in Design, Synthesis and Development of Novel Anticancer

and Antimalarial Agents
Ibrahim El-Tantawy El-Sayed
President of Japan Society for the promotion of Science Alumni Association in Egypt
(JSPSAAE), Professor of Organic & Medicinal Chemistry, El-Menoufia University, Faculty of
Science, Chemistry Department, Shebin El koom, Egypt
This lecture will be focused on two parts. In the first part, we will present diarylphosphonate
inhibitors for urokinase-type plasminogen activator (uPA) with anticancer activity. Urokinase-
type plasminogen activator (uPA) is a serine protease which is situated on the cell surface and can
be bound to its receptor (uPAR). The role of uPA/uPARsystem in human cancer was
demonstrated (Thromb. Haemostasis 2005, 93, 641).We have designed and developed
peptidicdiphenylphosphonate inhibitors of uPA.. A first potent and selective lead compounds
were identified and a lead optimization program was started to modify the compounds to a small
non-peptidicdiarylphosphonate irreversible inhibitor of uPA (J. Med. Chem. 2006, 49, 5785,
ibid,J. Med. Chem. 2007, 50, 6638). Potent and selective uPA inhibition was obtained (IC50< 10
nM; selectivity toward a set of other trypsine like serine proteases more than 1000 fold).The
synthetic approach, structure activity relationship (SAR) and in vivo animal studies of these
selective inhibitors will be presented.
While the Part II of my lecture will deal with the development of neocryptolepine scaffolds as a
novel antimalarial active agents.As part of a larger project for developing more potent and safer
antimalarial lead compounds based on natural product, we have developed robust and efficient
synthetic method for the natural product alkaloid, neocryptolepine (J. Med. Chem. 52, 2979,
2009), ibid, 56, 1431, 2013) isolated from the shrub Cryptolepissanguinolenta used in Central and
West Africa in traditional medicine for the treatment of malaria. A lead optimization program
was started to modify the compound and a wide range of neocryptolepine analogues with
diversified frameworks and drug-like properties were synthesized. Potent and selective analogues
against malaria as well as cancer with IC50 in the low nanomolar range were obtained (Med.
Chem. Commun.5, 927, 2014), European Journal of Medicinal Chemistry 64, 498, 2013,
Medicinal Chemistry Research 25, 879, (2016).). The synthetic routes of these molecules, their
biological activities and proposed mechanism of action will be illustrated from both our own
research and literature.
26
New Therapeutic and Drug Delivery Methods for the Anterior Segment
of the Eye : from bench to clinic.
Hamdy Abdelkader
New Therapeutic and Drug Delivery Methods for the Anterior Segment of the Eye: from Bench
to Clinic School of Pharmacy and Chemistry, Kingston University London, UK Faculty of
Pharmacy, Minia university, Minia, Egypt.
Cataracts and corneal disorders are the primary causes of blindness worldwide with a massive
health and economical cost that is incurred to Medicare and NHS. Corneal ulcers are common
manifestations of a number of genetic (e.g. Familial corneal hypoesthesia), systemic (e.g.
diabetes) and ocular (e.g. viral, drug toxicity and surgical) diseases. The standard treatment of
corneal ulcers consists of a number of components including: maximizing preservative free
topical lubricants, use of topical antibiotics and protecting the corneal surface with a bandage
contact lens. These measures may be ineffective, and the outcome is often severe sight
impairment. Novel therapeutic modality of the opioid growth factor receptor
antagonistnaltrexone, formulation development of in situ gelling ocular films and clinical
evaluation for effective and safe treatment of impaired corneal ulcers of different origins will be
discussed. Further, Cataract or clouding of the human lens is the first cause of blindness
worldwide. The only available treatment is surgeries. Whilst the surgical removal of the lens and
replacing it with an artificial intra-ocular lens has been successful to reduce the blindness, these
surgeries are inaccessible for most of developing countries and have long waiting lists in
developed countries and associated with high health complications and high cost. The search for
anti-cataract drugs has been continuing for decades; some treatments no longer exist but
antioxidants are still of much interest. The talk will discuss the emerging role of the endogenous
dipeptide L-carnosine as a potential novel anti-cataract drug and phytosomes as lipid-based
carriers for enhanced Lcarnosine uptake by the outer coat of lipophilic corneal membranes and
delivering it to the lens.
27
Scientific Computing for Drug Discovery
Ahmed Farouk
Director of Bioinformatics Unit, CLAES, ARC. Director of Expert System Research and
Development Department, CLAES, ARC. Program Leader, Faculty of Computer Science, MSA.
Machine learning (ML) has proven in the last few years to be a valuable tool in drug design.
Consequently it has become a basic component in most programs and tools available for
researchers in this area of research. The importance of ML comes from its ability to induce and
predict under different conditions for both sequence and structure of ligand and target protein.
This work will concentrate on different techniques in ML to decide which is effective in solving
different problems such as virtual screening, docking and scoring.
28
Active Site Hydration, Thermodynamics and Drug Design
Khaled M. Elokely, Manal A. Nael
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta 31527,

Egypt
Water displacement from the proteins ligand binding pocket is usually associated with binding of
a drug-like molecule. This water displacement is accompanied with thermodynamics changes
which contribute to the overall protein-ligand thermodynamics. Energetic penalties are attributed
to displacement of conserved water in polar active site regions, while displacement of water
found in non-polar regions of the ligand binding pockets is usually favorable for ligand binding.
The SZMAP method of OpenEye Scientific Software is used to calculate the binding free
energies and the corresponding thermodynamic components of active site water. The binding free
energy of explicit water molecules that are placed within different positions at the binding site are
computed to differentiate the locations of the active site with large affinity for polar or nonpolar
ligand substituents. In this method canonical water model and a modified one (uncharged water)
lacking any electrostatic interaction with the protein are used. This calculation is displayed as 3D
maps, one to show the regions with large putative occupancy of uncharged water, another one to
show the same property for the canonical water model, and a third one to show the regions in
which uncharged waters have the largest van der Waals interactions with the protein. Inspection
of these maps is informative about the spatial distribution of chemical groups that gives rise to
large ligand-target affinities. Regions deemed favorable for binding uncharged waters are putative
binding spots of nonpolar moieties. Conversely, regions showing large propensity for canonical
water are probable binding spots for polar and charged groups. More detailed information can be
extracted from the regions showing the largest van der Waals interaction energies with the
uncharged water molecules.
29
Synthesis and Medicinal Significance of Novel Heterocyclic Compounds

Containing Pyrazole Moiety
Somaia elkarim
Therapeutical Chemistry Department, Pharmaceutical and Drug Industries research Division

National Research Center
Pyrazole ring is an exciting nucleus. It successes to attract the interest of researchers towards
synthesizing its numerous derivatives such as pyrrolo pyrazole, pyridinyl pyrazole, pyrazoline
carbazide, aryl pyrazole carboxylic acid, pyrazolinone, pyrazole aryl ureas and quinolinyl
pyrazole compounds due to their wide range of biological activities. Several strategies including
metal-catalyzed reactions, microwave-irradiation and heating methods have been successfully
employed to afford these required pyrazole skeletons. Several pyrazole-based drugs have already
made their way to clinics and are successfully used against various disorders. The structure
activity relationship of the pyrazole compounds and molecular modeling indicated that the choice
of a suitable substituents including electron-donating, electron with drawing as well as some
heterocyclic ring systems on the basic skeleton represents a key role in regulating the biological
activities of the new synthesized compounds. Furthermore, since the simple synthetic procedures
enable the scientists to construct the core scaffolds of numerous marketed drugs, chemical and
biological studies should be continued on these pyrazole scaffolds hoping to get novel drugs of
various biological activities of high selectivity and efficacy and devoid of the side effects that
might be obtained by the parent drugs.
30
Application Of Heterocyclic Compounds In The Field Of

Chemotherapy
Maher A. El hashash
Professor of organic chemistry, chemistry department, faculty of science, Ain Shams university
Three membered heterocyclic compounds, for example: Oxitanes ,ethylene and propylene oxides
are primarily used as starting materials for variety of useful chemicals also have biological roles
metabolism and toxicity. On the other hand, B.azridines react with the hydroxyl group of
cellulose and used to import wet strength and abrasion cotton fibers to swell in water. Also
azridine reacts with phosphorus oxy-chloride and yielded triaziridyl phosphine oxide (APO)
(C2H4N)3PO which react with the hydroxyl groups cellulose and make textiles fire resistance
and also used under the name tepa as stirlant for male insects.Also it reacts with cyanutyl
chloride and yielded 2,4,6-triazitidyl triazine (tretamine) and used for stitlant mule insect.
Aziridine Derivatives also have many industrial uses.It is a toxic liquid, it reacts with the
hydroxyl groups of cellulose and used to impart wet strength and abrasion resistance to paper and
to decrease the tendency of rayon and cotton fibers to swell in water. Reaction of aziridine with
phosphorus oxychloride gives triaziridylphosphine oxide (APO) (C2H4N)3PO which also reacts
with the hydroxyl groups of cellulose and makes textiles fire resistant. This compound under the
name of tepa is used as a sterilizer for male insects. It exhibits physiological activity with
nitrogen mustard gas. Nitrogen mustards (NMs) form cyclic aminium ions (aziridiniumrings) by
intramolecular displacement of the chloride by the amine nitrogen. Thiirane is the name applied
for a three- membered ring comprising of one sulfur atom. It has been known for a long time.
Thiirane has also been designated as ethylene sulfide, episulfide, or thiacyclopropane. Thiirane
have not been found naturally and have many industrial uses.
Four membered rings are not as highly strained as the corresponding three membered rings, but
are more difficult to prepare by direct cyclization of straight chain intermediates. This is partly
because the atoms that must combine, unlike those that join to give a three-membered ring can
alter their relative position considerably under the influence of thermal motion. It is only when
the cyclizing atoms happen to be suitably oriented and the appropriate hard condition applied that
the ring can form. Azetidine, commonly known as trimethylenimine and occasionally as
azacyclobutane, was first obtained in pure form in 1899. It has many biological roles, The natural
penicillins, the first antibiotics to be used in medicine, contain the thiazole ring system or
azetidinone nucleus [-lactam ring]. The penicillin apparently act by interference with the
synthesis of the bacterial cell walls. It is though that they do this by reacting with an amino group
of an essential enzyme of the cell wall biosynthesis pathway. This reaction, which involves ring
opening of the -lactam and acylation of the amino group in activates enzymes.
Five-Membered Ring with One Hetero-atom, the doubly unsaturated five-membered heterocyclic
compounds have specific characteristics. Their chemical behavior resemble aromatic compounds
31
as well as non-aromatic dienes. However, substitution reactions are to be found rather than
addition reactions. The NMR spectra indicate a more or less strong aromatic ring current.
Porphin is the parent chemical compound for types of biochemically significant compounds
called porphyrins. The chemical formula of porphin is C20H14N4. Porphin is an organic
compound that is aromatic and heterocyclic since its chemical structure, essentially consists of
four pyrrole rings joined together by four methine (=CH) groups to form a larger macrocycle
ring. The compound itself is a solid.
Six-Membered Ring, Heterocyclic compound having six-membered ring containing one hetero-
atom (e.g., N, O & S) include pyridine, pyran and thiopyran.
The pyridine ring and its reduced forms (piperidine,dihydropyridine, and tetrahydropyridine) are
of wide spread natural occurrence, and are synthesized by plants, possibly by the way of amino
acids as precursors. Although the heterocyclic rings of pyridine derivatives are not synthesized by
higher animals; several of them are of the greatest importance in the cellular economy of animal
life (must be ingested by animal in their diets, in the form of vitamins). Perhaps the most
important pyridine derivatives are those which from the prosthetic groups of many enzymes
whose formation is the catalysis of oxidation reactions in the cells of both plants and animals.
These are called NAD (nicotinamide adenine dinucleotide phosphate). NADP is a phosphate ester
of NAD, and bears the additional phosphoric acid group on the adenine-linked ribose unit. In
combination with specific proteins, NAD and NADP form enzymes that participate in oxidation-
reduction reactions in living cells. The NAD portion of the enzyme alcohol dehydrogenase, for
example accept hydrogen from ethanol to form acetaldehyde.
32
Site Identification by Ligand Competitive Saturation (SILCS) in Drug

Discovery
Atef Abd El-Monem Abd El-Hafez
Professor and head of Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University,
Assuit, Egypt
Structure-based drug design (SBDD), which involves the discovery and optimization of small
molecules that bind to a target with known 3D structure, is of central relevance to medicinal
chemistry. Computational methods have important roles to play in SBDD from early to late
phases in a typical drug discovery project resulting in time and cost savings. Docking followed by
scoring of millions of compounds may be used to identify novel lead compounds in the early
stages of SBDD campaigns. Toward overcoming present limitations in fragment-based
computational drug design, a new method that combines ideas from experimental fragment-based
drug discovery with all-atom explicit-solvent MD is now available. The method (SILCS: Site
Identification by Ligand Competitive Saturation) involves computationally immersing a protein
in an aqueous solution simultaneously containing different types of small molecules, with each at
a concentration of 1 M. The protein + small molecule + water system is then subjected to
multiple MD simulations allowing for competitive binding of the small molecules to the protein.
Snapshots from the MD trajectories are combined to generate 3D probability maps (FragMaps)
that reveal what types of functionalities bind most strongly to different parts of the protein
surface. Because they are generated from MD simulations, SILCS FragMaps incorporate both
protein mobility, with a Boltzmann distribution of conformations, and atomic-level solvation
effects, thereby yielding FragMaps that represent rigorous free energy distributions. Notably, the
method requires minimal time, labor, and materials compared to experimental approaches. SILCS
FragMaps, when visualized as isosurfaces in conjunction with a protein may potentially be used
to guide the development of inhibitors at a particular site on the protein surface.
33
Protein Engineering an Effective Strategy to Improve Catalytic, Kinetic,

and Thermodynamic, Properties of Industrial Enzymes
Mohamed A. Abdel Naby
Department of Chemistry of Natural and Microbial Products , National Research Center, Cairo,
Egypt.
Enzymes are of great importance in the development of industrial bioprocesses. Insufficient

kinetic stability of enzymes restricts its application in many industrial processes. While there have
been reports in the literature that chemical modification modulates protein stability, however
mechanistic details still remain uncertain. The recent techniques for improving thermostability of
industrial enzymes will be described. A number of solutions found by nature to increase protein
stability will be compared and illustrated by a short example. I will give an overview how this
knowledge can be used for the molecular redesign of proteins to increase protein stability for
possible research or industrial applications. Evaluation of enzyme thermostabilization in terms of
thermodynamic parameters including kcat, kcat/Km , values (D) entropy (S*) , enthalpy of
deactivation (H*). free energy of activation (G*), G*ET and G*ES values will be
presented.
34
Production and characterization of antimicrobial compound produced

by Streptomyces atrovirens H33
Donia H Sheir
Department of Natural and Microbial Product, Research Division of Pharmaceutical and Drug
Industries, National Research Centre, Dokki, Cairo, Egypt
Streptomyces atrovirens was isolated from soil samples in Egypt and showed broad spectrum
antimicrobial activity. It was identified as Streptomyces atrovirens (strain H33) based upon16S
rRNA gene sequencing. It was deposited in the GenBank database under accession number of
KJ435269. Streptomyces atrovirens (strain H33)was cultivated by submerged fermentation
bioreactor to produce the antimicrobialmetabolites. Purification and identification of
antimicrobial compound was carried out. The antimicrobial compound exhibited low cytotoxic
effect on human epithelial HL cells.
Key words: 16S rRNA, bioreactor; cytotoxicity, HPLC MS/MS, Streptomyces atrovirens H33
35
Advanced microbial tools for antibiotic discovery
Bahgat Fayed
The upsurge of bacterial resistance in the last decade makes the need to discover new antibiotics
inevitable. The pharmaceutical industry has produced a remarkable range of antibiotics in the last
century to come over the resistance problem. Most of the discovered antibiotics were found in the
golden era of the antibiotic discovery between 1929 and 1962, then only two novel antibiotic
classes, were introduced 40 years later. On the other hand during the same period, the bacterial
resistance was rising to high levels. It is clear that discovery of new antibiotics is facing crisis and
new strategies to develop new antibiotics are urgently needed. In this presentation we will address
this critical situation and the advanced microbial tools currently used in Europe for the discovery
of new antibiotics.
36
Penicillin G Acylase in Drugs' Industry
Marwa Ibrahim Wahba
Penicillin G acylase (PGA) is a key enzyme in the beta-lactam antibiotics industry which, in
2012, constituted 57% of the global antibacterial drug market with a value of $24.8 billion. PGA
catalyzes the synthesis of 6-aminopenicillanic acid (6-APA) and 7
aminodesacetoxycephalosporanic (7-ADCA) after hydrolyzing penicillin G, cephalosporin G,
and related compounds. These 6-APA and 7-ADCA are the precursors for the synthesis of many
of the new semi synthetic penicillins and cephalosporins, respectively. Moreover, PGA can also
catalyze the acylation of 6-APA and 7-ADCA to produce such new semi synthetic antibiotics.
PGA can be produced from several microorganisms including bacteria, fungi, and yeast. The
economic value of the microbially produced PGA will be greatly enhanced after its stabilization
as this stabilization process will significantly increase the enzyme's half life and will also help the
enzyme to withstand the extreme industrial operating conditions. PGA has been stabilized
through many approaches including chemical modifications, protein engineering, and medium
engineering. PGA has also been stabilized through immobilization onto different supports. The
immobilization process offers additional advantages when compared to the other stabilizing
techniques. Immobilization of enzymes onto solid supports facilitates the separation of the
enzymes from their reaction products; hence, the contamination of the final products will be
minimized and the recovered enzymes could be reused in a continuous industrial operation
37
Drug Discovery and Development
Ahmed A. El-Rashedy
The identification of novel therapeutics is a long and complex process that involves a wide range
of scientific disciplines and techniques. Firstly , The discovery process includes target selection
as well as the identification of potential lead compounds using high throughput screening and/or
in silico screening methods. Lead optimization eventually produces a clinical candidate.
Secondly , the development phase, is focused on determining the clinical utility of a candidate
compound in patients. Clinical trials designed to determine the safety and efficacy of candidate
compounds provide data to support regulatory approval. Our lecture will be focused on the
challenges on drug discovery and how we can overcome these challenges .
Keywords
Drug development overview, Drug design problem , future trends
38
(The Whole Day)
39
P: 1
Constructing white light emitting metal-organic frameworks by post-

synthetic modification
Reda M. Abdelhameed
Researcher-Applied Organic Chemistry Department, National Research Centre
Metal-organic frameworks (MOFs) are crystalline materials consisting of metal ions and
organic linkers. MOFs have a potential application in gas storage, gas separations,
chemical sensing, ion exchange, drug delivery, removal of heavy metals from aqueous
solutions, catalysis, and as photoactive and luminescent materials [1]. One of the most
attractive features of MOF materials is the possibility of their post-synthetic modification
(PSM) [2], particularly by the functionalisation of linkers to produce materials with new
functionalities. Lanthanide-organic frameworks (Ln-MOFs) have promising applications
due to their unique luminescence properties. However, it is still very challenging to
develop suitable Ln-MOF materials capable of producing color tunable and white-light
emission. Moreover, a higher coordination number and more flexible coordination
geometry of lanthanide ions make it even harder to obtain stable porous lanthanide MOFs
[3].
Our main research interest focuses on PSM as a route to introduce active sites for light-
emitting devices into MOFs. [4] Here, we construct new MOF doped with lanthanide
(Tb3+ and Eu3+ ) to generating white light emitting materials. The samples were
characterised by powder XRD, EDS elemental analysis and solid-state NMR and the
luminescent properties of the materials were studied.
[1] R.J. Kuppler, D.J. Timmons, Q. Fang, J. Li, T.A. Makal, M.D. Young, D. Yuan, D.
Zhao, W. Zhuang, H. Zhou, Coord. Chem. Rev., 2009, 253, 30423066.
[2] R.M. Abdelhameed, L.D. Carlos, A.M.S. Silva and J. Rocha, Chem. Commun., 2013,
49, 5019.
[3] J. Rocha, L.D. Carlos, F.A.A. Paz, D. Ananias, Chem. Soc. Rev., 2011, 40, 926-940.
[4] R.M. Abdelhameed, L.D. Carlos, A.M.S. Silva, J. Rocha, New J. Chem., 2015, 39,
4249-4258.
40
P: 2
pH-controlled Release System for Curcumin based on Functionalized

Dendritic Mesoporous Silica Nanoparticles
Khaled EA AbouAitah1, Farghali AA2 , Anna Swiderska-Sroda3, Witold Lojkowski3 , Abdel-Fattah
M Razin1 and Khedr MH2
1Department of Medicinal and Aromatic Plants Research, Pharmaceutical and Drug Industries
Research Division, National Research Centre (NRC), Dokki, Giza, Egypt.
2Materials Science and Nanotechnology Department, Faculty of Postgraduate Studies for

Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt.
3Laboratory of Nanostructures for Photonic and Nanomedicine Institute of High Pressure

Physics, Polish Academy of Sciences, Warsaw, Poland
Mesoporous silica materials are promising drug delivery systems, especially in case of
poorly water-soluble drugs. Curcumin (Cur) has proven effective for several
pharmacological activities including anti-inflammatory, antioxidant, antimicropeal,
hepatoprotective, and anticancer activities. In the present work two types of mesoporous
silica nanoparticles were evaluated as a Cur carrier for controlled release of this
anticancer natural pro-drug: MCM-41 (Two Dimensional) and KCC-1 (Three
Dimensional), both functionalized with aminopropyl groups. KCC-NH2 and MCM-NH2
contained a similar amount of Cur (24.5% and 23.9%, respectively). In vitro experiments
have shown that both materials effectively release Cur and the cumulative release was
enhanced for low acidity (pH=2.5). At low acidic pH (2.5), the KCC-1 sample released
higher amount (up to 19%) of curcumin compared to MCM-41 (14%). Thus it is possible
to achieve controlled, long-term and effective pH-stimulated release of curcumin from
aminefunctionalized mesoporous silica nanoparticles. This finding opens the way for
their application for controlled curcumin delivery in cancer disease because of the acidic
tumor environment, increase its stability and lead to an increase of the Cur
bioavailability. Moreover, the KCC-1 three dimensional mesoporous silica seems to be a
more promising nanocarrier compared to the commonly used MCM-41 material.
Keywords
Drug delivery system; pH-controlled release; MCM-41 and KCC-1; Mesoporous silica
nanoparticles and curcumin
41
P: 3
New Potent SARS-CoV 3C-Like Protease Inhibitors Derived from

Thieno[2,3-d]-pyrimidine Derivatives.
Abd El-All AS1, Atta SM1, Roaiah HM1, Awad EM1, Abdalla MM2.
1
and Drug Industries, National Research Centre, Dokki, Giza, Egypt.
2
Research Unit, Saco Pharm. Co., 6 October City, Egypt.
2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1) condensed with

carbaldehydes 2a,b to give the respective thienopyrimidines (3a,b), which reacted with
phosphoryl chloride and hydrazine hydrate to afford the respective pyrimidinohydrazines
(4a,b). Compound 4a condensed with acetophenone under Vilsmeier conditions to afford
the formylated pyrazolopyrimidine 6. Condensation of 4a with active methylenes
produced the respective pyrazolopyrimidines (7-11). Besides, 4a condensed with succinic
anhydride and with phthalic anhydride, yielding the pyrrolidine-2,5-dione 12 and the
isoindoline-1,3-dione 13, respectively. Moreover, 4a reacted with isatin to afford the
hydrazono-indolin-2-one 14. Structural elucidations for the new thienopyrimidines were
based upon compatible analytical and spectroscopic results. Eleven of the new
compounds were tested and found active against influenza A neuraminidase virus
(H3N2). Compounds 12 and 13 were the most potent.
Keywords:
Acid anhydrides; Active methylenes; Influenza virus (H3N2) inhibition; Structural

elucidation; Tetrahydrobenzothienopyrimidines
42
P: 4
Mesoporous Silica Materials in Drug Delivery System: pH/Glutathione-

Responsive Release of Poorly Water-Soluble Pro-drug Quercetin from
Two and Three-dimensional Pore-Structure Nanoparticles
AbouAitah KEA1, Farghali AA2 , Swiderska-Sroda A3, Lojkowski W3 , Razin AM1 and Khedr MH2
1Department of Medicinal and Aromatic Plants Research, Pharmaceutical and Drug Industries
Research Division, National Research Centre (NRC), Dokki, Giza, Egypt
2Materials Science and Nanotechnology Department, Faculty of Postgraduate Studies for

Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt
3Laboratory of Nanostructures for Photonic and Nanomedicine, Institute of High Pressure

Physics, Polish Academy of Sciences, Warsaw, Poland
Quercetin (Quer) is one of natural products (pro-drugs), presenting pharmacological

properties such as: anti-oxidant, anti-inflammatory and anti-cancer activities. However,
poor solubility of the Quer causes its poor bioavailability, and consequently reduces its
therapeutic efficiency. To manage this problem, different actions are undertaken, among
other drug delivery systems (DDSs) are investigated. The objective of present work was
to evaluate potential applications of silica nanoparticles as quercetin nanocarriers and to
investigate the influence of pH conditions and glutathione (GSH, as non-redox process)
concentrations on quercetin release. Two types of mesoporous silica nanoparticles:
MCM-41 (2D arrangement of pores) and KCC-1 (3D arrangement of pores) were
synthesized and then functionalized by amino-groups. Immersion-evaporation method
was used to load the Quer in nanoparticles. Several analysis techniques were used (e.g.
electron microscopy, X-Ray diffraction, Zeta potential, simultaneous thermal analysis-
connected to FTIR and many more). Obtained results indicated that both types of silica
nanoparticles were successfully loaded with quercetin, and that the Quer present in silica
mesopores had a non-crystalline structure. Loading capacity of functionalized MCM-41
was slightly higher than functionalized KCC-1 (29.11 wt% and 26.49 wt%, respectively).
This difference could be attributed to the differences in the morphology structures such as
surface area and pore volume property. From in vitro release and kinetics studies, the
results showed that quercetin release from both materials was pH-GSH-silica type
nanoparticles-dependent. In summary, it can be stated that pH/GSH-stimuli release of
quercetin was achieved using MCM-41 and KCC-1 amine-functionalized mesoporous
silica nanoparticles as a drug carriers. Therefore both investigated nanomaterials could be
beneficial for long-term release
43
P: 5
Synthesis, biological evaluation and molecular modeling study of some

Thiadiazolodiazepine analogues as a new class of neuromuscular
blocking agents
Hussein I. El-Subbagh,1 Adel S. El-Azab,2,3 Ghada S. Hassan,1 Shahenda M. El-

Messery,4 Alaa A.-M. Abdel-Aziz,1,2 Kamal E.H. El-Taher 5
1Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University,
Mansoura 35516, Egypt
2Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University,
P.O.Box 2457, Riyadh 11451, Saudi Arabia

3Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo
11884, Egypt
4Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura
University, Mansoura 35516, Egypt

5Department of Pharmacology, College of Pharmacy, King Saud University, P.O.Box 2457,
Riyadh 11451, Saudi Arabia
The synthesis, biological evaluation and molecular modeling study of 6,7-dihydro-[1,3,4]

thiadiazolo[3,2a][1,3]diazepine analogues as new class of neuromuscular blocking agents
are described. The new compounds act via competitive mechanism with ACh which
could be reversed by the anticholinesterase Physostigmine. Compounds GS-53 (30) and
AAH1 (33) induced dose-dependent neuromuscular blockade with onset time of 3 and 10
min, ED 0.15 and 0.36 mmol/kg i.p., respectively, in rats. Compound 30 proved to be as
twice as potent as 33 with rapid onset and shorter duration (P < 0.05). Docking prole of
30 and 33 closely resembles HIE-124 (3), in a7b2 nAChR receptor. Molecular modeling
analysis indicated that hydrogen bonding to Thr120 and Thr124 beside hydrophobic
interactions play effective role incorporating the active ligands to nAChR. The obtained
model could be useful for further development of new skeletal muscle relaxants.
44
P: 6
Rat Bone Marrow Mesenchymal Stem Cells Differentiation Into Germ

Cells In Vitro
El- Husseny, A. Bossila1; Bahgat, A. El-Fiky2; yousry, A.Dowidar1; Aly, M. El Refy1
And Hussein, S. Hussein1
1. Biotechnology Department, Faculty of Agriculture-Al-Azhar University-Cairo-Egypt

2. Animal Biotechnology Department, Genetic Engineering and Biotechnology Institute,
University of Sadat City.
Azoospermia is present in approximately 1% of all men, and in approximately 15% of

infertile men. Azoospermia is one of the most complex diseases in male infertility. It is
defined as the complete absence of spermatozoa upon examination of the Semen.
Azoospermia may result from a lack of spermatozoa production in the testes or from an
inability of produced spermatozoa to reach the emitted semen infertile men. Study have
reported that bone marrow stem cells co-culture with extracts obtained from testicular
tissue are able to trans differentiate to Leydig Cells , thereby improving the production
of testosterone and derivation of male germ cells in vitro. The present study aimed to
investigate the differentiation potential of Mesenchymal stem cells into male germ cells.
Mononuclear cells were separated from bone marrow blood cells obtained from wistar
strain female rats and cultivated in cell culture. Mesenchymal stem cells were
characterized by their adhesiveness and fibroblast like appearance. The floating cells
were aspirated off and mesenchymal cells were proliferated for 3passage using Dulbecco
Modified Eagle Medium (DMEM) supplemented with 10% FCS. Testicular tissue
extracts obtained from male rats cultivated with mesenchymal stem cells to promote the
differentiation of bone marrow stem cells to Leydig Cells and gamete production in vitro.
The obtained data showed the expression of testosterone biosynthetic marker STAR and
17B-HSD3 by using Quantitative real time PCR (qPCR). Our findings provide direct
evidence that rat bone marrow mesenchymal stem cells can differentiate to Leydig Cells
and identify mesenchymal stem cells as a potential source of male germ cells that could
sustain sperm production.
Key Word: Mesenchymal Stem Cells, Testicular tissue extract and male germ cells
45
P: 7
Recovery of Female Infertility by Bone Marrow Mesenchymal Stem Cells in Rats
M.Elbehary1, El-Fiky, B.A. 2, Y. A. dwadar1, A.M. El-rify1

Animal Biotechnology Department, Genetic Engineering and Biotechnology Research
Institute, University of Sadat City, Egypt.
Chemotherapeutic treatment affects young patients occasionally on infertility as in

premature ovarian failure. Studies showed that stem cells have the ability to repair
ovarian damage induced by chemotherapeutic agents. The present study aimed to
investigate the repair efficacy of bone marrow mesenchymal stem cells for
chemotherapy-induced ovarian failure. Female Wistar rats were administered with
cyclophosphamide (CTX) for consecutive 15 days followed by administration of
(BMSCs) for 3 days. Ovaries were excised and blood serum was collected. After that,
ovaries were histologically sectioned for accounting and categorization of
follicles,vaginal smear were collected every morning all over the experiment to observe
estrus cycle and the sexual hormones; FSH and E2 were measured in blood serum
samples. The ovaries which treated with CTX were stimulated after administration of
BMSC. The amount of ovarian follicles were increased, the regularity of rat's estrus cycle
was improved and improvements in sexual hormones were noticed. The study concluded
that (BMSCs) has a recovery effects in recovery of chemotherapy-induced ovarian
failure.
Key Words: Premature Ovarian Failure, Cyclophosphamide and Bone Marrow

Mesenchymal Stem Cells.
46
P: 8
Synthesis, Docking Study, and Cytotoxic Evaluation of Novel Thiopyrimidines and
Their Condensed Sulfonamide Analogs
Mohamed F El-Shehry
Department of Pesticide Chemistry, National Research Centre, Dokki, Egypt
A novel series of thiopyrimidines and their condensed derivatives bearing a sulfonamide

moiety were synthesized using 4-oxo-N-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-
sulfonamide 1a,b as a key starting compounds. The cytotoxic activities of the synthesized
compounds showed in vitro significant antitumor activities when compared with
doxorubicin as a reference drug. Furthermore, a comparative docking study into PTK
(PDB: 1t46) has been done involving flexible docking for
potential binding affinities of various derivatives to find out the binding orientation of
these novel analogs into their binding site. Some of the newly synthesized compounds
showed considerable binding affinities. The structures of the novel derivatives confirmed
on the bases of micro-analytical and spectral data.
[1] J. Weschel, K. Haglund, E. M. Haugsten, Biochem. J. 2011, 437, 199.
[2] J. J. Marin, F. Sanchez de Medina, B. Castao, L. Bujanda, M.R. Romero, O.

Martinez-Augustin, R. D. Moral-Avila, O. Briz, Drug Metab. Rev. 2012, 44, 148.
[3] R. C. DeConti, Semin. Oncol. 2012, 39, 145.
47
P: 9
Synthesis and antimicrobial activity of some potent substituted

thioxothiazolidin4-ones
Amira Said Abd-el-all
Department of Natural and Microbial Products, Research Division of Pharmaceutical and

Drug Industries, National Research Centre, Dokki, Giza, Egypt
5-Chloroisatin-2,3-dione (1) condenses with 3-substituted rhodanine 2a-c to

give the respective thioxothiazolidin-4-one derivatives 3a-c which is treated with
secondary amines and formaldehyde to offered Mannich bases 4a-d. Compound 4a-d also
could be obtained by authentic method. Reduction of compound 3a-c with Zn/ AcOH
produced the respective thioxothiazolidin-4-one 6a-c. Compound 6b reacts with
secondary amines and formaldehyde to yield 7a, b. While, chlorination of compound 6b
with POCl3 yielding compound 8, which in turn reacts with different amines to give
piperidine or triazino derivatives 9, 10. Moreover, compound 3a reacts with different
secondary amines produce thiazolin derivatives 11a, b, which is reduced by Zn/AcOH to
give compound 12a, b, also, compound 12a, b could be obtained by authentic method
.Condensation of compound 12a, b with hydrazine hydrate or phenyl hydrazine produced
the respective 13a, b, and 14 a, b derivatives. On the other hand, compound 12a reacts
with morphiline or piperazine in presence of formaldehyde to yield the corresponding
Mannich base 15a, b. The effect of the seventeen new compounds 1, 3a-c, 6 b, c, 8, 10a,
b, 11a, b 13a, 14a ,b and 15a, b on two types strains of bacteria and two fungi were
studied.
48
P: 10
Synthesis of New oxazine and oxazocine derivatives and Evaluation of

their Antiproliferative Potency against Different Cancer Cell Lines
Nagwa M. Fawzy1 , Hanaa A. Tawfik1, Shwekar I. El Naem1, Enas M. Awad1, Magde S.
Aly2
1
Chemistry of Natural and Microbial Products Department, National Research Center,
Dokki, Cairo, Egypt.
2
Zoology Department, Faculty of Science, Beni-Suef University, Egypt.
A new one-pot procedure was affording for the synthesis of novel oxazocine derivatives
4a, b by using of a three-component condensation reaction: aldehyde 1, Meldrums acid
2, and isocyanate derivatives 3a, b in dichloromethane at room temperature. A novel
isocyanate-based four-component reaction between an aldehyde 1, Meldrums acid 2, an
isocyanate derivatives 10a-c and an aromatic phenol derivative 9a, b/ and or p- anisidine
9c was provided oxazocine derivatives 11a-i. A novel one-pot procedure of three-
component reaction for the preparation oxazine-derivatives 13a-d were described by
heating a mixture of an anthranilic acid, aldehyde 1, and an isocyanate derivatives 12a-d
in methanol. All of the new prepared compounds were evaluated as anti-cancer activity
against human liver HEPG2, breast MCF-7, prostate PC3 cell lines. The anticancer
activity results indicated that the synthesized products 4b, 11b, 13b, 11e and 11i showed
growth inhibition activity against two of the tested cell lines (HEPG-2 and PC3) but with
changing intensities extents against Doxorubicin as a reference to the anticancer drug.
Our results also showed that all compounds did not any activity against human breast
MCF-7 cells. The results yielded a theoretical reference for the exploration of new anti-
cancer agents and may be useful for the design of new chemotherapeutic drugs.
49
P: 11
A Novel Multi-Component Reaction of Indoles and Formyl

Furochromone was Described for the Synthesis of Indoles Derivatives
with Expected Antitumor Activity
I.F.Zaeid1, A. M. Nasef2, N.M. Fawzy2, A. M. Soliman3, M.M.E-Baroudy2
1Organic Chemistry Department, Menophia University, Egypt.
2Natural Products Department, National Research Center, Dokki, Cairo, Egypt.
3Theraputical Chemistry Department, National Research Center, Dokki, Cairo, Egypt.
A new strategy for synthesis of 3-diaryl indoles (4a-c) was developed through FeCl3 as
Lewis acid catalyzed three-component aza- Friedel-Crafts reactions of aldehyde (1)
tertiary aromatic amines (2) and indole derivatives (3a- c) in one-pot. A simple and
efficient synthesis of compounds (5a-d) were achieved via Schiff's base reaction of 3-
diaryl indole (4b) with various aldehydes namely benzaldehyde, hydroxylbenzaldehyde,
isonicotinaldehyde and furoaldehyde respectively. Compounds (6a-c) were obtained by
the reaction of compound (4c) with different halide compounds namely 3-bromoprop-1-
ene, iodoethane and benzyl chloride respectively. The reaction of cyclohexyl isocyanide
(7) with aldehyde (1) and indole (3c) has given compound (8) in one step. While, the
reaction of cyclohexyl isocyanide (7) with aldehyde (1) has given compound (9) which
reacted with indole (3c) yielded compounds (10). Five selected indole derivatives 4a, 4b,
5b, 5d and 6a were subjected to a screening system for investigation of their antitumor
potency against breast (MCF7) and liver (HEPG2) cell lines. Moreover, the biochemical
effects of the selected indole derivatives on some enzymes such as aspartate and alanine
aminotransferase (AST and ALT) and alkaline phosphatase (ALP), in addition to
albumin, globulins, creatinine, total lipids, cholesterol, triglycerides and bilirubin in
serum of mice were studied in comparison to 5-Flurouracil and Doxorubicin. The
antitumor activity results indicated that most of the selected indole derivatives showed
moderate growth inhibition activity against liver (HEPG2) cell line. Moreover, compound
(6a), showed anti-proliferative activity against both breast and liver cell lines.
Keywords: Cyclohexyl isocyanide, Aza-Friedel-Crafts reaction and Schiffs base. Breast

and Liver Cancer cell lines
50
P: 12
Synthesis of Novel Acetamide Derivatives and Evaluation of their

Antiproliferative Potency against Different Cancer Cell Lines
Hanaa M. Roaiaha, Khadiga M. Ahmedb , Nagwa M. Fawzya , Joanna Wietrzykc ,Agata
Pawlikc, Mamdouh M. Alid, Abdel Mohsen Solimane .
a
b
Chemistry of Natural Compounds Department, National Research Centre, Giza, Egypt.
c
Experimental Oncology Department, Polish Academy of Sciences, 12, R. Weigla Str.
53-114 Wroclaw, Poland.
d
Biochemistry Department, National Research Centre, 33 El Beehouth St., Dokki, Giza,
Egypt.
e
Therapeutic Chemistry Department, National Research Centre, 33 El Beehouth St.,
Dokki, Giza, Egypt.
The objective of this research was to prepare a new acetamide derivatives with anticancer
activities. p-Toluenesulfonic acid catalyzed the one-pot, a multicomponent reaction
involving furochromone carboxaldehyde I, cyclohexyl/or phenylisocyanates 1a,b and
amine derivatives (namely: 4-anisidine; 2-anisidine; 4-nitroaniline,4-aminopyridine
respectively ) 2a-d for the synthesis of (4,9-dimethoxy-5-oxo-5H-furo[3,2-g]chromen-6-
yl)acetamide derivatives 3a-h have been described. Also, This methodology was afforded
2-(pyridin-4-ylimino)acetamide derivatives 4a-h at the reaction of aldehyde derivatives
(namely: 1H-indole-3-carbaldehyde; 2-(thiophen-2-yl)-1H-indole-3-carbaldehyde; 3-
methoxy-5,6-diphenyl-1H-indole-2-carbaldehyde; 3-hydroxy-5,6-diphenyl-1H-indole-2-
carbaldehyde; 8-oxo-2,3-diphenyl-8H-furo[2,3-g]chromene-7-carbaldehyde respectively)
IIa-e with cyclohexyl/or phenylisocyanates 1a,b and p-minopyridine. The in vitro
antiproliferative activity evaluation of the prepared compounds (3a-h) have been assessed
against four different human tumor cell lines including human liver HepG2, breast MCF-
7, lung A549 and colon HCT116 cancer cell lines. The results revealed that all the
prepared compounds did not show any antiproliferative effect towards A549 and
HCT116 cell lines. Although compounds 3f, 3d and 3c showed growth inhibitor activity
on both HepG2 and MCF-7 cancer cell lines with IC50 values near to the standard drug,
compound 3e was found to be more potent than the doxorubicin in both liver and breast
cancer cell lines. On the other hand, 2-(pyridin-4-ylimino)acetamide derivatives 4a-h
51
were subjected to a screening system for investigation of their antiproliferative potency

against human promyelocytic leukemia (HL-60), lung cancer (A549), breast
adenocarcinoma (T-47D) and human colon cancer (LoVo) cell lines in comparison to the
traditional anticancer drug cisplatin. Results showed that the highest in vitro cytotoxic
activity against HL-60 cell line (IC50 lower than 12 g/ml) revealed compounds: 4c, 4d,
4e, 4g. These compounds were chosen for testing their antiproliferative activity against
A549 (lung cancer), T-47D (breast adenocarcinoma) and LoVo (human colon cancer
cells) cancer cell lines. Compounds (4c and 4e) showed the highest activity against all
tested cancer cells.
In this research work, a novel acetamide derivatives were prepared.
Keywords: Multicomponent reaction; acetamide derivatives; p-toluenesulfonic acid;

antiproliferative potency; cancer cell.
52
P: 13
Efficient Synthesis of 9-Substituted Acridine Derivatives as Potential

Anticancer Candidates
Yasser M. Shaker
Division of Pharmaceutical and Drug Industries, Department of Chemistry of

NaturalandMicrobial Products, National Research Centre, Dokki, 12622, Cario, Egypt.
e-mail: yabdelrahman@yahoo.com
Acridine/acridone derivatives are considered to be a promising class of compounds of

potential anticancer drugs.1 Different synthetic methods are reported for the preparation
of target acridine units followed by functionalization reactions or modification of natural
acridone alkaloids which possess interesting anticancer activity. The importance of
acridines in chemotherapy is attributed to their high chemical and biological stability and
their ability to bind strongly with DNA and RNA. 2 This makes disorder for the
biological function of living cells. The intercalation of acridines with DNA is due to -
stacking with base pairs of double-stranded nucleic acids. Indeed, the first synthetic drug
for DNA-intercalating type is amsacrine 1 (m-AMSA). 3,4 This lead drug showed
clinical efficiency as anticancer agent. The aim of our work is to utilize modern synthetic
organic chemistry for functionalization and modification of acridine skeleton by
attachment of 5- or 6-memebered heterocyclic rings to acridine at position 9 via different
linkers. The synthesized acridine derivatives 2 and 3 will expected to play important rule
as drug candidates in cancer therapy.
53
References
1. Cholewiski G., Dzierzbicka K., Kolodziejczyk A. M., Pharmacological Reports

2011, 63, 305-336.
2. Belmont P., Dorange I. Expert. Opin. Ther. Patents, 2008, 18, 12111224.
3. Atwell G. J., Cain B. F., Seelye R. N. J. Med. Chem., 1972, 15, 611615.
4. Denny W. A. Curr. Med. Chem., 2002, 9, 16551665
P :14
Design Of New Opioid Modulators Using Structure- and Ligand-Based Virtual
Screening
Manal A. Nael1, Vedanjali Gogineni2 and Khaled M. Elokely1

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta
31527, Egypt
2
National Center for Natural Products Research and Department of BioMolecular
Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi
38677, United States
Opioid drugs are designed to modulate one or more of the four major subtypes of opioid
receptors, the , , , and nociceptin receptors. They have ~70% sequence identity with
differences at N and C termini. This high degree of structural similarities makes it
difficult to selectively target one of the subtypes. Lack of proper understanding of ligand
interaction with opioid receptor at molecular level made target-based drug design hard.
We aimed to take advantage of the of the crystal structures of opioid receptors that have
been released to understand the molecular determinants of ligand binding and to discover
new active opioid modulators. In this study, we managed to design drug-like molecules
that bind selectively to the receptor. Towards this aim, we built a structure-based
pharmacophore and 3D shape models using the molecular information of the receptor
antagonist, JDTic. ZINC database of purchasable compounds, ~22 Million compounds,
was subjected to multiple drug-likeness filters, followed by combined ensemble docking
experiments and pharmacophore/shape-based filters to select 40 compounds for
biological testing. One of the selected compounds exhibited preferential activity against
receptor, 40 nM, over receptor, 400 nM.
54
P : 15
Synthesis, Anticancer Activity and Molecular Docking Study Of Novel 1, 3-
Diheterocycles Indole Derivatives
Eslam R El-Sawy1, Heba M Abo-Salem1, Khalied Mahmoud2, Eman S Zarie3, Amira M

El-Metwally4 and Adel H Mandour1
1
Chemistry Department of Natural Compounds, National Research Centre, Egypt,
2
Pharmacognosy Department, National Research Centre, Egypt, 3 Nanochemistry and
nanoengineering, Faculty of Engineering, Institute for Materials Science, University of
Kiel, Kaiserstrasse, Germany, 4National Organization for Drug Control and Research,
Egypt.
DNA topoisomerases I (TopoI) have been identified as important targets for cytotoxic
drugs as they play role in regulating the topological rearrangement of DNA during
transcription, replication and recombination. Therefore, the inhibition of such enzymes
attracts the attention of many researchers over many years [1]. On the other hand, Indole
which is the potent basic pharmacodynamic nucleus has been reported to possess a wide
variety of biological properties viz, anti-inflammatory [2]. The present work aimed to
synthesize some new 1, 3-diheterocyles indolyl derivatives and study their cytotoxic
activity. In addition, explore the probability of the most promising antiproliferative
compounds to inhibit TopoI enzyme theoretically via molecular docking study. Reaction
of ethyl 2-(3-formyl-1H-indol-1-yl)acetate (1) with 2-cyanoacetic acid hydrazide, 3-
amino-5-pyrazolone and 2'-acetyl-2-cyanoacetohydrazide in an equal molar ratio led to
the formation of compounds 2, 6, 8 and 10, respectively, which in turn reacted with
another molecule of 2-cyanoacetic acid hydrazide and/or 3-amino-5-pyrazolone (1:1
molar ratio) to give novel series of 1,3-dipyrazole indole derivatives 3, 7, 9 and 11,
respectively. On the other hand, Knoevenagel condensation of 1 with malononitrile gave
ethyl 2-(3-(2, 2-dicyanovinyl)-1H-indol-1-yl) acetate (11). Reaction of 11 with 2-
cyanoacetic acid hydrazide, 3-amino-5-pyrazolone, hydrazine hydrate, urea, thiourea
and/or guanidine yielded 1, 6-diaminopyridine 12, pyrano(2,3-c)pyrazole 14, pyrazole 16
and pyrimidine derivatives 18a-c, respectively. Reaction of the latter compounds with 3-
amino-5-pyrazolone furnished a novel series of 1, 3-diheterocycle indole derivatives 13,
15, 17 and 19a-c, respectively. Ten new target compounds 3, 6, 8, 10, 13, 15, 17 and 19a-
c were tested for in vitro antiproliferative activity against A-549, MCF7, HCT-116 and
HEPG2 cancer cell lines. In addition, molecular docking study of the most promising
antiproliferative compounds against human DNA Topoisomerase I (PDB ID: 1T8I)
theoretically is discussed. Compounds 3, 6, 8 and 17 showed potent in vitro
antiproliferative activity. Docking scores of the latter compounds were observed better
than co-crystalline ligand. Further work is recommended to confirm the inhibition of
TopoI in a specific bioassay
55
Reference:
1. Hsiang YH, Hertzberg R, Hecht S, Liu L. Camptothecin induces protein-linked
DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 1985; 260:
14873-8
2. Guerra AS, Malta DJ, Laranjeira LP, Maia MB, Colao NC, de Lima-Mdo C,
Galdino SL, Pitta-Ida R, Gonalves-Silva T. Tumor- and organ-dependent
infiltration by myeloid-derived suppressor cells Int Immunopharmacol 2011; 11:
816-26
P : 16
Biosynthesis, Anticancer Screening and Molecular Docking Studies of Novel Anti-
tubulin Fungal Metabolites
Iman A. Y. Ghannama, Hanaa M. Roaiaha, Adel S. Girgisb, Mamdouh M. Alic, Mona

M. Hannad, Sally S. El-Nakkadya, Russell J. Coxe,f
a
Chemistry of Natural and Microbial Products Department, National Research Centre,
Dokki, Cairo, Egypt, bPesticide Chemistry Department, National Research Centre,
Dokki, Cairo, Egypt, cBiochemistry Department, National Research Centre, Dokki, Cairo,
Egypt, dPharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University,
Cairo, Egypt, eOrganic and Biological Chemistry Department, School of Chemistry,
University of Bristol, Bristol, UK, fInstitute of Organic Chemistry, Leibniz Universitt
Hannover, Schneiderberg 1B 30167, Germany
E-mail: iman.youssef.ghannam@gmail.com
The biosynthetic pathway of fusarochromene-A, a novel secondary metabolite isolated

from the sugarcane fungal pathogen, Fusarium sacchari, was investigated using feeding
13 13
isotopic labelling studies. C-1 and C-2 labelled tryptophan were synthesised and fed
separatly to the fungal culture by day 5 of inoculation. Fusarochromene-A was then
isolated by HPLC mass directed purification and it was found that the labelling position
in fusarochromene-A in poisitons, C-14 and C-13 respectively. Therefore, the feeding
experiments suggested that tryptophan is the precursor for the fusarochromene
biosynthesis. Fusarochromene-B was also first isolated from the fungal culture of
Fusarium. In vitro anticancer screening was done for the 2 fusarochromenes against
different 60 cancer cell lines at NCI - US. It was found that Fusarochromene-A and -B
revealed relatively moderate anticancer activities against renal (UO-31) and prostate (PC-
56
3) cancer cell lines. Molecular modelling study was initiated in order to determine the
mode of action for fusarochromenes. Fusarochromene-A and -B were docked into
colchicine binding site of tubulin and it was revealed that they interacted with the two
hydrophobic centres of colchicine binding site region in the -chain of tubulin similarly
to the lead colchicine. Therefore, they have the ability to inhibit tubulin assembly and act
as microtubule destabilizing agents. A tubulin polymerization assay was done to confirm
in vitro anti-tubulin activity and it was found that both fusarochromene-A and -B
exhibited relatively moderate activities against tubulin.
P: 17
Bone Marrow Mesenchymal Stem Cells Restore Male Infertility in Azoospermic

Mice
Wrshana, T.A. 1, El-Fiky, B.A. 2, Dwidar Y. A. 1and El-Rify A.M. 1

1 Biotechnology Department, Faculty of Agriculture, University of Al-Azhar, Cairo.
Egypt.
2 Animal Biotechnology Department, Genetic Engineering and Biotechnology Research
Institute, University of Sadat City, Egypt.
Email: t.wrshana@gmail.com
Recovery of spermatogenesis has been show in patients treated with chemotherapy against
different malignancies resulting in azoospermia. The present study was designed to
investigate the ability of bone marrow mesenchymal stem cells to restore fertility in
induced azoospermic mice following cyclophosphamide administration. The study was
carried out on 70 male mice with an average body weight ( 23.425.1) obtained from
Theodore Bilhariz Research Institute, Ministry of Scientific Research, Giza, Egypt. Mice
were acclimatized two weeks. 10 mice were subjected for bone marrow blood cells
separation from tibia and femur bones for mesenchymal stem cells separation and the
other 60 mice were divided into three groups; G1 (20 mice): normal control, G2 (20 mice):
Cyclophosphamide induced untreated group and G3 (20 mice) induced treated group with bone
marrow mesenchymal stem cells. Induction of azoospermia was obtained by a loading dose 50
mg/kg and after 24 h, a rotating dose 8 mg/kg for fourteen days constantly. Blood and testicular
tissue samples were separated from all studied groups for hormonal and histological study Data
obtained from the study showed that, follicle stimulating hormone, E2 , testosterone and histology
of testicular tissue in azoospermic mice induced with cyclophosphamide group showed a
significant improvements compared to azoospermic induced untreated and normal groups.The
57
results concluded that bone marrow mesenchymal stem has the ability to restore male infertility in
induced mice experimental animal model.
Key Words: Azospermic mice, Cyclophosphamide and bone marrow mesenchymal stem cells
P: 19
Anticancer Catechol-Benzothiazole Conjugates; Design, Laccase-Catalyzed Green
Synthesis and Cytotoxic Evaluation against MCF-7 Cell Line
Heba T. Abdel-Mohsena and Uwe Beifussb
a
Natural and Microbial Products Department, Pharmaceutical Industries Research
division, National Research Centre, Cairo, Egypt
b
Bioorganische Chemie, Institut fr Chemie, Universitt Hohenheim, Garbenstr. 30,
Stuttgart, D-70599, Germany.
Breast cancer is regarded as the most common type of cancer in women. Every year more
than half a million new cases with breast cancer are diagnosed worldwide. Despite the
tremendous progress that has been achieved in cancer therapy over the last decades, the
currently available drugs suffer from serious disadvantages that limit their use, such as
lack of selectivity, toxicity and resistance. For these reasons, the development of novel
anti-tumor agents is still a point of scientific research. Green synthesis of pharmaceutical
active molecules represents a challenging issue of modern chemistry. One of the most
beneficial protocols to achieve this target is the enzyme-catalyzed transformation. In this
study, a series of catechol-benzothiazole conjugates were synthesized by a laccase-
initiated domino transformation between catechols and benzothiazole derivatives using
aerial O2 as an oxidant in aqueous solvent system. The developed synthetic protocol
combines several steps in single transformation using laccase enzyme as a catalyst.
Moreover, the twelve principles of green chemistry are fulfilled. Evaluation of the
synthesized compounds in vitro against MCF-7 human breast adenocarcinoma cell line
revealed their efficient potential to control the cell proliferation with IC50 in the
micromolar level. Structure activity relationship was studied to enable further
development of this class of compounds.
58
P:20
Synthesis and Anticancer Evalution of Novel 2,2,6,6-Tetramethyl-4-Piperdone
Dervities
Mahmoud N. M. Yousif ,N. M. Yousif , Hanem M. Awad
Photochemistry Department, National Research Centre, Egypt
*E-mail: mahmoud_nabil18@yahoo.com
,2,6,6-Teramethyl-4-piperidone derivative I reacts with 2 moles of aromatic aldehyde and

thiosemicarbazide to afford pyrazolo(4,3-c)pyridine derivatives IIa-c. The acetylation of
compound IIc with acetic anhydride afford mono and triacetylated products IIIa-b.
Compound I reacts with 2 moles of aromatic aldehyde in ammonium acetate to afford
3,7-diazabicyclo[3.3.1]nonan derivative IVa-c. Anticancer evaluation of the synthesized
compound is performed.
O
2ArCHO
N
R
I
NH2CSNHNH2 NH4OAC
Ar R
N
N S
N
HN O
NH2
Ar Ar N Ar
H
IIa-c
IVa-c
Ac2O
Ar
N S
N
NR3
NR1R2
Ar
IIIa-b
a, R1=COCH3, R2=R3=H
b, R =R =R3=COCH3
1 2
59

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The 1st International Drug Discovery Workshop

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The 1st International Drug Discovery Workshop

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The 1st International workshop on Drug discovery 2016 Book of Abstracts

The 1st International workshop on Drug

Drug Discovery workshop

Website Developer: Mohammed Abd Elhay

Dr : Fatma Abd AL Aleem Dr Weam Salah Goda

Dr Ayman Sweed Dr Huda Refat

Drug Discovery Workshop

10.00-10.30 a.m. Opening

10.30-11.00a.m Prof. Dr. Feras Alalia

Development of Drug Target Prof. Dr. Naidu Subbarao

11.30-12.00a.m. Lipase-Catalyzed Kinetic Prof. Dr. Hassan Aboul-

12.00-12.30p.m. Rational Design Of Small Prof. Dr. Khaled H. S.

12.30-01.00p.m. Coffee Break

01.00-01.30 p.m. Biopolymer for industrial, Prof. Dr. Mahmoud Ahmed

systems Abd Elghafar

Polymers and pigments

01.30-02.00a.m. Towards A Comprehensive Prof. Dr. Ameen Farouk

2.00-`02.30p.m. Computer-aided drug Dr. Mahmoud Ibrahim

02.30-03.00 p.m. A Journey in Design, Prof. Dr. Ibrahim Tantawy

03.00-03.30 p.m. New Therapeutic and Drug Prof.Dr. Hamdy Abdelkader

03.30-04.30p.m Lunch Break & Poster

09.00-10.00 a.m. Registration

10.00-10.30a.m. Scientific Computing for Prof. Dr. Ahmed Farouk

Head of Expert System

10.30-11.00a.m. Active site hydration, Prof. Dr. Khaled M. Elokely

11.00-11.30a.m. Synthesis and Medicinal Prof. Dr. Somaia elkarim

11.30-12.00p.m. Application of heterocyclic Prof. Dr. Maher A. El

12.00-12.30 p.m. Site Identification by Ligand Prof. Dr. Atef A Abdel-Hafez

01.00-01.30p.m. Coffee Break

01.00-01.20 pm Protein Engineering an Prof. Mohamed Abd elnabi

01.20-01.40 pm Production and Dr. Donia H Sheir

01.40-02.00 pm Advanced Microbiol tools Dr Bahgat Ezzat

02.00-2.20 pm Penicillin G Acylase in Dr Marwa Wahba

02.20-02.40pm Drug Discovery and Dr Ahmed El Rashedy

Kindly shut off your mobiles during the session.

Prof. Dr. Mahmoud Ahmed Abd Elghafar

Prof. Dr. Khaled M. Elokely

10.30-11.00a.m. Betting on Natural Products: Cytotoxic Homoisoflavones

12.00-12.30p.m. Rational Design Of Small Molecule Immune

New Hall (01.00-03.30pm)[II]

Prof. Dr. Hassan Aboul-Enein

Prof. Dr. Naidu Subbarao

01.00-01.30 p.m Biopolymer for industrial, medical and drug delivery

Prof. Dr. Ameen Farouk Mohamed Fahmy

Faculty of Science, Ain Shams University, Egypt

02.00-`02.30p.m. Computer-aided drug discovery of LTB4 inhibitors

Dr. Mahmoud A. A. Ibrahim

Head of CompChem Lab, Chemistry Department, Faculty of

02.30-3.00 p.m. A Journey in Design, Synthesis and Development of

Prof .Dr : Amira Said

10.00-10.30a.m Scientific Computing for Drug Discovery

Prof. Dr. Khaled H. S. Barakat

Prof. Dr. Ibrahim Tantawy

Dr. Mahmoud Ibrahim

Constructing white light emitting metal-organic frameworks by post-synthetic

Researcher Applied Organic Chemistry Department, National Research Centre

pH-controlled Release System for Curcumin based on Functionalized Dendritic

Khaled EA AbouAitah , Farghali AA , Anna Swiderska-Sroda , Witold Lojkowski , Abdel-

Department of Medicinal and Aromatic Plants Research, Pharmaceutical and Drug

New Potent SARS-CoV 3C-Like Protease Inhibitors Derived from Thieno[2,3-d]-

Department of Natural and Microbial Products, Research Division of Pharmaceutical

Mesoporous Silica Materials in Drug Delivery System: pH/Glutathione- Responsive

AbouAitah KEA , Farghali AA , Swiderska-Sroda A, Lojkowski W , Razin AM and Khedr