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    Quantitative Structure Activity Relationship: Guided By: Mr. Shivendra Singh Raghuvanshi Assistant Professor

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    Anjelica Tricton
    QSAR relates the biological activity of a molecule to its physicochemical properties using mathematical equations. Key parameters used in QSAR include lipophilicity parameters like partition coefficients, electronic parameters like Hammett constants, and steric parameters like Taft constants. QSAR can be used to understand a drug's mechanism of action, predict biological activity and toxicity, optimize lead compounds, and apply to environmental chemistry problems.

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    Quantitative Structure Activity Relationship: Guided By: Mr. Shivendra Singh Raghuvanshi Assistant Professor

    Uploaded by

    Anjelica Tricton
    86 views18 pages
    QSAR relates the biological activity of a molecule to its physicochemical properties using mathematical equations. Key parameters used in QSAR include lipophilicity parameters like partition coefficients, electronic parameters like Hammett constants, and steric parameters like Taft constants. QSAR can be used to understand a drug's mechanism of action, predict biological activity and toxicity, optimize lead compounds, and apply to environmental chemistry problems.

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    It contains molecular drug designing and QSAR study parameters

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    QSAR studies

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    QSAR relates the biological activity of a molecule to its physicochemical properties using mathematical equations. Key parameters used in QSAR include lipophilicity parameters like partition coefficients, electronic parameters like Hammett constants, and steric parameters like Taft constants. QSAR can be used to understand a drug's mechanism of action, predict biological activity and toxicity, optimize lead compounds, and apply to environmental chemistry problems.

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    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    86 views18 pages

    Quantitative Structure Activity Relationship: Guided By: Mr. Shivendra Singh Raghuvanshi Assistant Professor

    Uploaded by

    Anjelica Tricton
    QSAR relates the biological activity of a molecule to its physicochemical properties using mathematical equations. Key parameters used in QSAR include lipophilicity parameters like partition coefficients, electronic parameters like Hammett constants, and steric parameters like Taft constants. QSAR can be used to understand a drug's mechanism of action, predict biological activity and toxicity, optimize lead compounds, and apply to environmental chemistry problems.

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    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 18

    QSAR

    Quantitative Structure activity Relationship

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

    1 Modern Institute Of Pharmaceutical sciences 4/12/2019


    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.

    2 Modern Institute Of Pharmaceutical sciences 4/12/2019


    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.

    3 Modern Institute Of Pharmaceutical sciences 4/12/2019


    Physico-chemical parameters :
    Partititon coefficient

    Hammet’s electronic parameter

    Tafts steric parameter and Hansch


    analysis
    Pharmacophore modeling and docking
    techniques.

    4 Modern Institute Of Pharmaceutical sciences 4/12/2019


    5 Modern Institute Of Pharmaceutical sciences 4/12/2019
    LIPOPHILIC PARAMETERS
     Lipophilicity is the partitioining of the
    compound between aqueous and non-aqueous
    phase.

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

    6 Modern Institute Of Pharmaceutical sciences 4/12/2019


     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.

    7 Modern Institute Of Pharmaceutical sciences 4/12/2019


    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.

    8 Modern Institute Of Pharmaceutical sciences 4/12/2019


    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)

    9 Modern Institute Of Pharmaceutical sciences 4/12/2019


     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.
    10 Modern Institute Of Pharmaceutical sciences 4/12/2019
    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.

    11 Modern Institute Of Pharmaceutical sciences 4/12/2019


     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 .

    12 Modern Institute Of Pharmaceutical sciences 4/12/2019


     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.

    13 Modern Institute Of Pharmaceutical sciences 4/12/2019


    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

    14 Modern Institute Of Pharmaceutical sciences 4/12/2019


    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

    15 Modern Institute Of Pharmaceutical sciences 4/12/2019


     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.

    16 Modern Institute Of Pharmaceutical sciences 4/12/2019


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

    17 Modern Institute Of Pharmaceutical sciences 4/12/2019


    18 Modern Institute Of Pharmaceutical sciences 4/12/2019

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