QSAR Based Study of Derivatives of Triazine Against The Enzyme Dihydrofolate Reductase

Abstract

Enzyme level inhibition, a technique being used for the rational development of drug has been used for dihydrofolate reductase, an enzyme found in the tumor cells has been the target of anticancer drugs. Quantum chemical reactivity descriptors such as heat of formation, total energy, steric energy, HOMO energy, LUMO energy, absolute hardness and electronegativity have been used to develop QSAR model of the inhibitors of the enzyme, dihydrofolate reductase. The inhibitors used are 25 triazine derivatives. The inhibitory activities in the terms of log 1/C of various derivatives against the enzyme, dihydrofolate reductase has been taken from literature. The values of various descriptors have been evaluated by using Win MOPAC 7.21 software with the help of PM3 method. Multiple linear regression analysis has been made with the help of above mentioned descriptors using the same software. The best model out of the various models developed with the help of PM3 calculations has the correlation coefficient, r²as 0.73825 and the cross-validation coefficient, r²cv as 0.688095 and has been chosen as the QSAR model. Thus prediction of inhibitory activity of this series of derivatives can easily be done with the help of the QSAR model developed.