CURRICULUM VITAE

DUDEKULA. DASTAGIRI
C/O Dr. Ahmed Kamal, Deputy Director
Indian Institute of Chemical Technology, Tarnaka, Hyderabad-500 607,
Andhra Pradesh, India.Phone: +91-40-27160123 Ext. 1633
Mobile: +91-9490237930, Fax: +91-40-27193189
Email: girichem1@gmail.com

OBJECTIVE
• To pursue post-doctoral research position in the area of Organic
Synthesis/Medicinal Chemistry/Chemical Biology that enables me to upgrade my
research knowledge and skills to contribute efficiently towards the development of
multi-disciplinary research.
EDUCATION
• Ph. D. in Organic and Medicinal Chemistry (2005-2010)
Indian Institute of Chemical Technology (IICT), Hyderabad, India.
Research Supervisor: Dr. Ahmed Kamal, Deputy Director, Indian Institute of
Chemical Technology (IICT), Hyderabad, India.
Thesis Title: “Synthesis and Apoptosis Inducing Ability of Pyrrolobenzodiazepine
Conjugates and Heterocyclic Chalcones”
• M. Sc., Chemistry (2000-2002)
College of Arts and Science, Sri Krishnadevaraya University, Anantapur, India.
• B. Sc., Maths, Physics and Chemistry. (1995-1998)
SARM Degree College, Allagadda, Sri Krishnadevaraya University, Anantapur, India.
ANALYTICAL TECHNIQUES
• Spectroscopy: Acquisition and analysis of 1D (1H, 13C), 2D (COSY, NOESY) NMR, IR,
UV and analysis of mass spectra (EI, ESI, FAB and MALDI).

• Chromatography: Experience in flash chromatography, preparative HPLC and TLC

using various column packing, GC and LC-MS.
• Other Relevant Experience: Computer software: MS Word, Power Point, ChemDraw,
preparation of research reports and manuscripts.

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HONORS & AWARDS
• Awarded Senior Research Fellowship (SRF) from the Council of Scientific and Industrial
Research (CSIR), New Delhi, Govt. of India (2007).

• Awarded Junior Research Fellowship (JRF) from the Council of Scientific and Industrial
Research (CSIR), New Delhi, Govt. of India (2005).
• National Eligibility Test for lectureship (conducted by CSIR, 2004).

RESEARCH WORK
• Five years of research experience as part my Ph. D degree under the supervision of Dr.
Ahmed Kamal, Deputy Director, Chemical Biology, Division of Organic Chemistry-I,
Indian Institute of Chemical Technology, Hyderabad, A. P., India.
• Designed and synthesized a series of new 2,5-diaryloxadiazole linked pyrrolo[2,1-c][1,4]
benzodiazepine conjugates and evaluated for anticancer activity, cell cycle effects and
apoptosis inducing ability.
• Synthesized a series of imidazo/benzimidazothiazole linked to pyrrolo[2,1-c][1,4]
benzodiazepine analogues as potential anticancer agents.
• Designed and synthesized Imidazothiazole-chalcone derivatives as anticancer and
apoptosis inducing agents.
• Designed and synthesized a number of new anilino substituted pyrimidine sulfonamides
as anticancer agents
• synthesized a new combrestatin/isoxazoline-galactoside prodrugs for potential
application in selective chemotherapy of solid tumours by ADEPT, GDEPT and PMT
strategies
• Prepared a number of novel isoxazole-quinazolinone conjugates as cytotoxic and anti-
tubulin agents
• Designed and synthesized a number of novel isoxazole-benzthiazole/benzimdazole
conjugates as anti-proliferative agents.

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CONFERENCES ATTENDED
• 3rd Mid-Year Symposium of the Chemical Research Society of India, from25th and 26th
July 2008, Department of Medicinal Chemistry, National Institute of Pharmaceutical
Education and Research (NIPER), Punjab, India.

• 12th CRSI National Symposium in Chemistry & 4th CRSI-RSC Symposium in Chemistry
from 4-7 of February, 2010 at NIPER & IICT, Hyderabad, India.
PROJECTS HANDLED
• Advanced Centre for Treatment, Research & Education in Cancer, Mumbai:

Team member in the completion of a collaborative research project between IICT and
Advanced Centre for Treatment, Research & Education in Cancer, Mumbai, for the
development of new cancer leads (Duration: Three years).

LIST OF PUBLICATIONS
1. “Synthesis, anticancer activity and mitochondrial mediated apoptosis inducing
ability of 2,5-diaryloxadiazole pyrrolobenzodiazepine conjugates”

Ahmed Kamal*, D. Dastagiri, M. Janaki Ramaiah, E. Vijaya Bharathi, J. Surendranadha

Reddy, G. Balakishan, Pranjal Sarma, S. N. C. V. L . Pushpavalli, Manika Pal-Bhadra,
Aarti Juvekar, Subrata Sen, Surekha Zingde.

(Bioorg. Med. Chem. 2010, 18, 6666).

2. “Synthesis of imidazothiazole-chalcone derivatives as anticancer and apoptosis

inducing Agents”
Ahmed Kamal*, D. Dastagiri, M. Janaki Ramaiah, J. Surendranadha Reddy, E. Vijaya
Bharathi, Chatla Srinivas, S. N. C. V. L. Pushpavalli, Dhananjaya Pal, Manika Pal-
Bhadra.

(Chem Med Chem 2010, 5, 1937).

3. “Base free monosulfonylation of amines using tosyl or mesyl chloride in water”

Ahmed Kamal*, J. Surendranadha Reddy, E. Vijaya Bharathi, D. Dastagiri.
(Tetrahedron Lett. 2008, 49, 348).

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4. “Design, synthesis, and biological evaluation of 3,5-diaryl-isoxazoline/isoxazole
pyrrolobenzodiazepine conjugates as potential anticancer Agents”
Ahmed Kamal*, J. Surendranadha Reddy, M. Janaki Ramaiah, D. Dastagiri, E. Vijaya
Bharathi, M. Ameruddin Azhar, Farheen Sultana, S. N. C. V. L . Pushpavalli, Manika
Pal-Bhadra, Aarti Juvekar, Subrata Sen, Surekha Zingde.

(Eur. J. Med. Chem. 2010, 45, 3924).

5. “Synthesis and biological evaluation of anilino substituted pyrimidine linked

pyrrolobenzodiazepines as potential anticancer agents”
Ahmed Kamal*, J. Surendranadha Reddy, M. Janaki Ramaiah, E. Vijaya Bharathi, D.
Dastagiri, M. Kashi Reddy, S. N. C. V. L . Pushpavalli, and Manika Pal-Bhadra.
(Bioorg. Med. Chem. Lett. 2010, 20, 5232).

6. “Quinazolinone linked pyrrolo[2,1-c][1,4]benzodiazepine(PBD) conjugates: Design,

synthesis, and biological evaluation as potential anticancer agents”
Ahmed. Kamal*, E. Vijaya Bharathi, M. Janaki Ramaiah, D. Datagiri, J. Surendranadha
Reddy, A. Viswanath, Farheen Sultana, S. N. C. V. L . Pushpavalli, Manika Pal-Bhadra,
Aarti Juvekar, Subrata Sen, Surekha Zingde

(Bioorg. Med. Chem. 2010, 18, 526).

7. “Synthesis, anticancer activity and apoptosis inducing ability of anthranilamide-

PBD conjugates”
Ahmed Kamal*, E. Vijaya Bharathi, M. Janaki Ramaiah, J. Surendranadha Reddy, D.
Datagiri, A. Viswanath, Farheen Sultana, S. N. C. V. L . Pushpavalli, Manika Pal-
Bhadra, Aarti Juvekar, Subrata Sen, Surekha Zingde

(Bioorg. Med. Chem. Lett. 2010, 20, 3310).

8. “Design, synthesis and biological evaluation of imidazo pyridine/pyrimidine chalcone

derivatives as potential anticancer agents”
Ahmed Kamal*, J. Surendranadha Reddy, D. Dastagiri, E. Vijaya Bharathi.

(Med. Chem. Comm. 2010, In Press).

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 9. “Synthesis and biological evaluation of cinnamido linked pyrrolo[2,1-c][1,4]
benzodiazepine as atimitotic agents ”
Ahmed Kamal*, G. Balakishan, G. Ramakrishna, T.Basha Shaik, K. Sreekanth, M.
Balakrishna, Rajender, D. Dastagiri, Shasi V. Kalivendi.

(Eur. J. Med. Chem. 2010, 45, 3870).

10. “Design, synthesis and biological evaluation of combrestatin/isoxazoline-galactoside

prodrugs for potential application in selective chemotherapy of solid tumours by
ADEPT, GDEPT and PMT strategies”
Ahmed Kamal*, J. Surendranadha Reddy, E. Vijaya Bharathi, D. Dastagiri.

Bioorg. Med. Chem. (Manuscript under preparation).

11. “Design, synthesis and biological evaluation of 3,5-diaryl isoxazoline/isoxazole

linked 2,3-dihydroquinazolinone hybrids as potential anticancer agents”
Ahmed Kamal*, E. Vijaya Bharathi, J. Surendranadha Reddy and D. Datagiri. (Accepted,
Eur. J. Med. Chem. 2010).

12. “Design, synthesis and apoptosis inducing ability of new anilino substituted
pyrimidine sulfonamides as potential anticancer agents”
Ahmed Kamal*, D. Dastagiri, J. Surendranadha Reddy, E. Vijaya Bharathi.
(Bioorg. Med. Chem. Lett. Manuscript under preparation).

LIST OF PATENTS

1. “Imidazothiazole-Chalcone derivatives as potential anticancer agents and process

for the preparation thereof”
Ahmed Kamal, D. Dastagiri, J. Surendranadha Reddy, E. Vijaya Bharathi.
2121/DEL/09, (INDIA), PCT/IB2010/002544.
2. “Isoxazoline linked pyrrolo[2,1-c][1,4] benzodiazepine hybrids and the process for
the preparation thereof”
Ahmed Kamal, J. Surendranadha Reddy, D. Dastagiri, E. Vijaya Bharathi.
(International publication No. WO 2009/118748 A1).

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 3. “Quinazolinone linked pyrrolo[2,1-c][1,4] benzodiazepine hybrids and the process
for the preparation thereof”
Ahmed Kamal, E. Vijaya Bharathi, D. Dastagiri, J. Surendranadha Reddy.
(International publication No. WO 2010/058416 A1).

4. “Isoxazole/Isoxazoline/Combretastatin linked dihydroquinazolinone hybrids as

potential anticancer agents and process for the preparation thereof”
Ahmed Kamal, E. Vijaya Bharathi, J. Surendranadha Reddy, D. Dastagiri, A. Viswanath.
(International publication No. WO 2010/058417 A1).
REFERENCES
1. Dr. Ahmed Kamal, FNASc
Director grade scientist
Chemical biology Laboratory
Indian Institute of Chemical Technology
Hyderabad-500 607, AP, India
Phone No: +91-40-27193157
Fax: +91-40-27193189, 27160512
E-mail: ahmedkamal@iict.res.in

2. Dr. B. V. Subba Reddy, Scientist-E1

Division of Organic Chemistry-I
Indian Institute of Chemical Technology
Hyderabad-500 607, A. P. INDIA
Phone No: +91-40-27193535
E-mail: basireddy@iict.res.in

3. Dr. M. Venkateswara Rao, Scientist

Division of Organic Chemistry-I
Indian Institute of Chemical Technology
Hyderabad-500 607, A. P. INDIA
Phone: +91-040-27160123 Extn. 2635 (Off)
E-mail: mvrao@iict.res.in

PERSONAL PROFILE
 Date of Birth: 1st May, 1978
 Sex: Male
 Nationality: Indian
 Marital Status: Married

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RESEARCH SUMMARY

“Synthesis, anticancer activity and mitochondrial mediated apoptosis inducing ability of

2,5-diaryloxadiazole-pyrrolobenzodiazepine conjugates”

(Bioorg. Med. Chem. 2010, 18, 6666−6677)

Currently cancer is one of the causes of death and it is likely to become the most common
disease in the near future. It is well established that DNA is the target for many anticancer drugs
that are presently being used in the clinic. However, there are very few DNA-interactive agents
that bind to DNA with high sequence selectivity. DC-81 (1), an antitumor antibiotic produced
from Streptomyces species, belongs to the pyrrolo[2,1-c][1,4]benzodiazepine (PBD) class of
compounds that are potent inhibitors of nucleic acid synthesis.
R1
R2
O O O
H
BnO BnO NH2 BnO N
OMe (i) N (ii) N R3
H H
O
H3CO H3CO H3CO
12 13 14a−d

(iii)

N N N N
R 1 OH (iv) R1 OBn
O O

R2 OCH3 R2 OCH3
R 3 16a−d 3
R 15a−d
16a: R1 = H; R2 = F; R3 = H
16b: R1 = H; R2 = CF3; R3 = H
16c: R1 = OCH3; R2 = OCH3; R3 = OCH3
16d: R1 = H; R2 = OCH3; R3 = OCH3

Scheme 2. Reagents and conditions: (i) NH2.NH2.H2O, EtOH, reflux; (ii) substituted benzoyl chlorides, pyridine,
reflux, 30 min, 85−95%; (iii) POCl3, reflux, 1h, 80−87%; (iv) EtSH-BF3OEt2, CH2Cl2, 12 h, rt, 80−89%.

In search of new effective anticancer agents, we have synthesized a series of PBD

conjugates by linking a diaryloxadiazole moiety to the PBD (DC-81) scaffold through the stable
alkane spacers and evaluated their anticancer activity. The promising activity obtained, prompted
us to investigate their role in the cell proliferation and apoptosis of human melanoma cell line
(A375). Further, we also investigated the effect of these compounds on regulatory proteins of
cell cycle progression. Moreover, thermal denaturation studies are also carried out, these

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conjugates showed better DNA binding ability. The in vivo efficacy study of compound 4l
revealed that the ability to delay the tumor growth and retention of body weight in the PC-3
human prostate cancer xenograft model suggested that 2,5-diaryloxadiazole-PBD conjugates
have promising anticancer activity in the treatment of human cancer.
N N
Br () O NO2 CH(SEt)2
n R1 O () O NO2
(i) O n
CH(SEt)2
H3CO N
R2 OCH3 H3CO N
O 3
11a−c: n = 1−3 R O
17a−l

(ii)

N N
R1 O () O NH2
O n
CH(SEt)2

R2 OCH3 H3CO N
(iii) R3 18a−l O

N N
R1 O () O N H 19a−c: R1 = H; R2 = F; R3 = H
O n
19d−f: R1 = H; R2 = CF3; R3 = H
R2 OCH3 H3CO N 19g−i: R1 = OCH3; R2 = OCH3; R3 = OCH3
R3 19 j−l: R1 = H; R2 = OCH3; R3 = OCH3
O
19a−l: n = 1−3

Scheme 3. Reagents and conditions: (i) 16a−d, K2CO3, dry acetone, reflux, 24 h, 80−92%; (ii) SnCl2.H2O, MeOH,
reflux, 60 min, 70%; (iii) HgCl2-CaCO3, CH3CN/H2O (4:1), 8-12 h, 55−60%.

“Synthesis of Imidazothiazole-Chalcone Derivatives as Anticancer and Apoptosis Inducing

agents”
(Chem. Med. Chem. 2010, 5, 1937−1947)

Chalcones are open-chain flavonoids in which two aromatic rings are joined by a three
carbon α, β -unsaturated carbonyl system (1,3-diphenyl-2-propen-1-ones). We have synthesized
a new class of chalcones, wherein the B-ring has been replaced by an imidazo[2,1-b]thiazole
scaffold. Compounds 3c and 3d showed significant anticancer activity in the cell panel assay of
NCI and the cell viability assay and these two compounds (3c and 3d) also showed cytotoxicity
in MCF-7 cells at 4 μM concentration. The FACS analysis also showed more population in sub-
G1 phase indicating that these chalcone derivatives have apoptosis inducing ability. These
effects were accompanied by changes in expression of key proteins in the G1 phase of the cell
cycle. Further modulation of the expression and function of the cell cycle regulatory proteins

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provide the mechanism for the inhibition of growth. From the results, it was also observed that
there was down regulation of cyclins and up regulation of CDK4 that suggests cell cycle
blocking in the G1 phase. Further, it was observed that the G1/S check point associated tumor
suppressor proteins such as p53, p21, p27 and chk2 protein levels were up regulated that results
in the induction of cell cycle arrest in G1 phase. Moreover the balance between p53 and NF-kB
were found to control the cell cycle proliferation as reported in earlier studies. These studies also
support that the up regulation of p53 and concomitant down regulation of NF-kB in these
compounds ultimately leads to apoptosis. In this study an insight in the cell cycle regulatory role
as well as apoptotic inducing ability of these new chalcones was extensively examined. These
studies suggest that compound 3d is a potential candidate for detailed biological investigations,
particularly for the treatment of breast cancer. .
RII

O NH (i) N O
.HBr
Br + R NH R NH
RII S S
(ii)
1 2 3

O CHO
N (iii) N
+ RII R RII
RI CH3 R
S N S N
6a−f 5a−h 4a−h
6a = 3,4,5-trimethoxyphenyl (iv)
6b = 3,4-dimethoxyphenyl
6c = 2- pyrrolyl O R
6d = 2- thienyl N
I S
6e = 3,5-difluorophenyl R
6f = 3,4-benzodioxolyl N
RII
7a−p
7a : R = H; RI = trimethoxyphenyl; RII = 4-methoxyphenyl
7b : R = H; RI = trimethoxyphenyl; RII = 4-fluorophenyl
7c : R = H; RI = trimethoxyphenyl; RII = 2-thienyl
7d : R = H; RI = trimethoxyphenyl; RII = trifluoromethyl
7e : R = H; RI = trimethoxyphenyl; RII = 3,4-dimethoxyphenyl
7f : R = H; RI = 3,4-dimethoxyphenyl; RII = trifluoromethyl
7g : R = Me; RI = trimethoxyphenyl; RII = 4-methoxyphenyl
7h : R = Me; RI = trimethoxyphenyl; RII = 4-fluorophenyl
7i : R = Me; RI = trimethoxyphenyl; RII = 2-thienyl
7j : R = H; RI = 2-pyrrolyl; RII = 4-methoxyphenyl
7k : R = H; RI = 2- thienyl; RII = 4-methoxyphenyl
7l : R = H; RI = 3,5-difluorophenyl; RII = 4-methoxyphenyl
7m : R = H; RI = 3,4-benzodioxolyl; RII = 4-methoxyphenyl
7n : R = H; RI = 3,4-benzodioxolyl; RII = 4-fluorophenyl
7o : R = H; RI = 3,4-dimethoxyphenyl; RII = 4-methoxyphenyl
7p : R = H; RI = 3,4-dimethoxyphenyl; RII = 4-fluorophenyl
Scheme 1. (i) acetone, reflux, 6-8 h; (ii) 2N HCl, reflux, 1h, 85−95%; (iii) POCl3, DMF, reflux, 1h, 70−80%;
(iv) 10 % aq. NaOH, 12 h, rt, 75−85%.

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“Design, synthesis and apoptosis inducing ability of new anilino substituted pyrimidine
sulfonamides as potential anticancer agents”
A series of new anilino substituted pyrimidine sulfonamides have been prepared. All the
compounds have been tested for anticancer activity against K-562 and A375 cell lines which
exhibited potent anticancer activity. These compounds would be a potential lead for their
development as new anticancer agents.
H
NH2 (i) N NH3+ NO3- H
R N N NO2
NH
N
NO2 NO2 (iii)
4 5 8a,b

+ (iv)
O (ii) O
H
R R N(CH3)2 R N N NH2
6a,b 7a,b
N
a: R = 3-Pyridyl
b: R = 3,4,5-trimethoxyphenyl 9a,b
O H H O
(v) N
S R N N R
9a,b + Cl R S
O
N O
10a−i
3a−i

Scheme 1. Reagents and conditions (i) H2NCN, HNO3, EtOH, reflux, 24 h, 58%; (ii) DMF-DMA,
toluene, reflux, 24 h, 72−75%; (iii) NaOH, n-butanol, reflux, 48 h, 60−62%; (iv) SnCl2.2H2O, HCl,
rt, 2 h, 80−82%; (v) K2CO3, dry DMF, rt, 6 h, 85−87%.

“Synthesis and Biological Evaluation of Imidazo/Benzimidazothiazole Linked Pyrrolo[2,1-

c][1,4]benzodiazepines as Potent Anticancer Agents”

A series of novel imidazo/benzimidazothiazole linked pyrrolobenzodiazepine (PBD)

conjugates have been synthesized. These conjugates (1a−c and 2a−f) have been tested for
anticancer activity against eleven human cancer cell lines and found to be very potent anticancer
agents with GI50 values in the range of <0.1−2.7 µ Μ . One of the conjugate 1a have shown
promising anticancer activity for individual cancer cell lines with GI50 values of <0.1 µ M.
Furthermore, the effects of the conjugates on A375 cell cycle have been studied and these PBD
conjugates might be useful for the development of anticancer agents with a greater therapeutic
potential for tumor suppression.

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 N
O () O N
n H
S N
H3CO N
1a−c n= 1−3 O
R
N
O () O N
n H
S N
H3CO N
2a−c R = H n= 1−3 O
2d−f R = F

“Synthesis and biological evaluation of anilino substituted pyrimidine linked pyrrolobenzo-

diazepines as potential anticancer agents”

(Bioorg. Med. Chem. Lett. 2010, 20, 5232−5236)

A new series of anilino substituted pyrimidine linked pyrrolobenzodiazepine conjugates

were prepared. The thermal denaturation studies showed that these conjugates have better DNA
binding ability compared to DC-81. Moreover, these binding studies were further validated by
restriction endonuclease BamHI digestion. Further, these PBD conjugates (1a–c and 2a, b)
showed good anticancer activity against 11 human cancer cell lines. The MTT proliferation assay
for the four promising compounds in A375 cells showed potent cytotoxicity at 4 µM. The FACS
analysis showed more population in sub-G1 phase indicating that all these PBD conjugates have
apoptosis inducing ability. It was observed from the results that the p53 levels were enhanced.
Pronounced increase in the levels of cytosolic cytochrome c and cleaved PARP was observed
particularly, it was more pronounced in case of 2b. Hence, these PBD conjugates induce
apoptosis by acting through the mitochondrial mediated pathway. Finally, it suggests that one of
the PBD conjugate like 2b would be a potential lead for their development as new anticancer
agents.

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 H H
R N N N O N
H
N O
MeO N
R1
O
1a: R = 3-pyridyl; R1 = H
1b: R = 3,4,5-trimethoxyphenyl; R1 = F
1c: R = 3,4,5-trimethoxyphenyl; R1 = H

O N
H H H
R N N N
MeO N
N O R1
O

2a: R = 3-pyridyl; R1 = H
2b: R = 3-pyridyl; R1 = F

“Base- free monosulfonylation of amines using tosyl or mesyl chloride in water”

(Tetrahedron Lett. 2008, 49, 348)

A mild and efficient procedure has been developed for the monosulfonylation of various
amines using mesyl or tosyl chlorides in water at room temperature to afford the corresponding
sulfonamides in high yields.
R2
H TsCl/MsCl
N 1 N
R R rt, Water R R1

R = aryl, benzyl, furfrryl, cycloalkyl; R1 = H; R2 = Ts, Ms

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