Quantative Structure Activity Relationship Of Inhibitors Of Glycolic Acid OxidaseAuthor(s): Pragnesh Kumar K.Marfatia, Rajesh Kumar Singh,Pashupati Prasad Singh
In order to avoid trial and error method in selecting a suitable drug, QSAR methods have provided a rational basis to the design of enzyme inhibitors. 90 derivatives of enzyme inhibitors, whose inhibitory potencies in term of PI50 are reported, have been used as study material for QSAR study. These derivatives are divided into five groups 1.Substituted glycolic acids, 2. Substituted oxyacetic acids, 3.Substituted glyoxylic acids, 4. Substituted-3-hydroxy-1H pyrrole-2,5-diones derivatives, 5. 4- Heterocyclic substituted 3-hydroxy-1H-pyrrole-2,5-diones derivatives. The QSAR study and MLR analysis have been collectively made, because the potency is reported in one unit and the target enzyme glycolic acid oxidase (GAO) is common to all. The study has been made with the help of seven descriptors in different combinations. 1.Heat of formation (ΔHf), 2.HOMO energy3. LUMO energy, 4. Absolute hardness (η) 5. Molecular weight (MW), 6.Electronegativity (χ) 7.Total energy (TE). This is perhaps for the first time when inhibitory potency has been related with quantum mechanical parameters, without any significance to structure of compounds. The values of descriptors have been obtained with the help of PC MODEL software using the semiempirical PM3 Hamiltonian. 32 multi linear regression models using different combinations of descriptors have been developed using the project leader program associated with CAChe software. The predicted activity is close to the observed activity and the correlation coefficient is above 0.80. The best QSAR models are obtained by MLR analysis using the combinations, (i) heat of formation, molecular weight and electronegativity, (ii) molecular weight, total energy and electronegativity.