QSAR

Quantitative Structure activity Relationship

Guided By : Presented by :
Riya Dhaigude
Mr. Shivendra singh raghuvanshi
B.Pharm 6th sem
Assistant Professor
0846py151067

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 What is QSAR ?
 QSAR is a mathematical relationship between a biological
activity of a molecular system and its geometric and chemical
characteristics.
A General formula quantitative structure activity relationship (QSAR) cean be
given by the following :
Activity = f (molecular of fragmental properties)
 QSAR attempts to find consistent relationship between
biological activity and molecular properties, so tha these
rules can be used to evaluate the activity of new compound.

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 PARAMETERS
 The parameter is the measure of the potential contribution of its group
to a particular property of the parent drug.

 Various parameters used in QSAR studies are

 Lipophilicparameters: partition coefficient, π-substitution constant

 Polarizabilityparameters: molar refractivity, parachor

 Electronic parameters: Hammetconstant, dipole moment.

 Steric parameters: Taft’s constant.

 Miscellaneous parameters: molecular weight, geometric parameter.

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 Physico-chemical parameters :
Partititon coefficient

Hammet’s electronic parameter

Tafts steric parameter and Hansch

analysis
Pharmacophore modeling and docking
techniques.

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 LIPOPHILIC PARAMETERS
 Lipophilicity is the partitioining of the
compound between aqueous and non-aqueous
phase.

 PARTITION COEFFICIENT :
P = [drug] in octanol / [drug] in water

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  P = [drug] in octanol / [drug] in water
 P is the measure of relative affinity of a molecule for the lipid and
aqueous phases in the absence of ionisation.
 1-octanol is most frequently used lipid phase in the
pharmaceutical research. This is because:
 It has a polar and non-polar region
 Po/w is fairly easy to measure
 Po/w often correlates well with many biological properties.
 It can be predicted fairly accurately using computational model.

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 Linear relationship between Logp and
log1/c
 Activity of drug is often related to P
Eg. Binding of drug to serum albumin
(Straight line – Limited range of log p )

 Binding increases as log p increases.

 Binding is greater for hydrophobic drugs.

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 Non linear relationship between Log p
and Log 1/c
Example 2 : General anaesthetic activity of ether.
(parabolic curve – larger range for log p value)

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  π-substituent constant or
hydrophobic substituent constants:

 The π-substituent constant defined by hanschand co-

workers by the following equation.
 px= log Px-log PH

 A positive πvalue indicates that the πsubstituent has a

higher lipophilicitythan hydrogen and the drug favoursthe
organic phase.
 A negative πvalue indicates that the πsubstituent has a
lower lipophilicitythan hydrogen and the drug favoursthe
aqueous phase.
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 ELECTRONIC PARAMETERS
 The electronic effect of various substituent will clearly have
an effect on drug ionisation and polarity.
 Have an effect on how easily a drug can pass through the cell
membrane and how strongly it caninteract with the binding
site.

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  Hammet’s constant :
 This is a measure of electron withdrawing or electron donating
ability of a substituent.

 sx= log (Kx/Kbenzoic)

 Electron Withdrawing Groups

 Equilibrium shifts Right & Kx> Kbenzoic

 Since sx= log Kx–log Kbenzoic, then s will be positive .

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  Hammett constant takes into account both resonance and
inductive effects; thus, the value depends on whether the
substituent is paraor metasubstituted
 -orthonot measured due to stericeffects.

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 STERIC PARAMETER
 It is a measure of the bulkiness of the group it represents and it effects
on the closeness of contact between the drug and receptor site.

 Taft’s steric constant :

 Measured of comparing the hydrolysis of substituted aliphatic esters
against a standard ester under acidic conditions.
Es = log kx – log ko

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 k represent the rate of hydrolysis of substituted ester against a standard
ester
ko represent the rate of hydrolysis of the parent ester.

 HANSCH ANALYSIS :
 Proposed that drug action could be divided into 2 stages:
 1) Transport & 2) Binding

 Each of these stages depend upon the physical and chemical

properties of the drug.
 Log 1/C = k1P = k2P2+ k3s + k4Es + k5

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  Look at size and sign for each component of the equation.
 Values of r <<0.9 indicate equation not reliable
 Accuracy depends on using enough analogs, accuracy of data, &
choice of parameters
 Applications: used to predict the activity of an as yet
unsynthesizedanalouge.

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 Application of QSAR
 Diagnosis of moa of drug.
 Prediction of activity.
 Prediction of toxicity.
 Lead compound optimization.
 Environmental chemistry.

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