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Introduction to Quantitative Structure-Activity Relationships | Chemistry

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A Brief Introduction to QSAR

Previously, we discussed structure-activity relationships in a previous medicinal chemistry article. A more mathematical approach, known as quantitative structure-activity relationships (QSAR), is what we will now consider. QSAR models are mathematical models which relate pharmacological or biological activity with the physicochemical characteristics (termed molecular descriptors) of a set of molecules. A general formula for a simple QSAR model is shown below:

Examples of biological activity that can be used for QSAR studies include:

Possible molecular descriptors that can be used for building QSAR models may include:

Molecular descriptors can be acquired from experimental data or through computational chemistry calculations (in silico).

Some notes regarding QSAR modelling:

Advantages and Disadvantages of QSAR

Advantages of predicting biological activity with quantitative structure-activity relationships modelling include:

Disadvantages of predicting biological activity with QSAR modelling include:

Applications of QSAR in Pharmacology and Medicinal Chemistry

Pred-hERG

Several drugs such as sertindole (antipsychotic) and terodiline (muscarinic antagonist) have been withdrawn from the market in many countries due to concerns regarding cardiotoxicity associated with hERG K+ channel blockage. Pred-hERG is a free computational tool, developed by Andrade et al, that incorporates QSAR models for predicting hERG K+ channel blockage and hence potential cardiotoxic properties of molecules. From a drug design and discovery perspective, tools such as Pred-hERG are useful since it can provide insight on the potential cardiotoxicity (or lack of) of potential drug candidates.

References
(1) Toropova, A. P.; Toropov, A. A.; Martyanov, S. E.; Benfenati, E.; Gini, G.; Leszczynska, D.; Leszczynski, J. Chemom. Intell. Lab. Syst.2012, 110 (1), 177–181.
(2) Gonella Diaza, R.; Manganelli, S.; Esposito, A.; Roncaglioni, A.; Manganaro, A.; Benfenati, E. SAR QSAR Environ. Res.2015, 26 (1), 1–27.
(3) Braga, R. C.; Alves, V. M.; Muratov, E. N.; Strickland, J.; Kleinstreuer, N.; Trospsha, A.; Andrade, C. H. J. Chem. Inf. Model.2017, 57 (5), 1013–1017.
(4) Braga, R. C.; Alves, V. M.; Silva, M. F. B.; Muratov, E.; Fourches, D.; Lião, L. M.; Tropsha, A.; Andrade, C. H. Mol. Inform.2015, 34 (10), 698–701.

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