Drug–receptor interaction‐based quantitative structure–activity relationship of tetrahydroimidazodiazepinone

Abstract

AbstractLog P, solvent‐accessible surface area (SASA), total energy, bond length, and bond strain of the most favorable H‐bond formed between drug and receptor; and quantum chemical descriptor ΔE‐based quantitative structure–activity relationship (QSAR) study of tetrahydroimidazodiazepinone derivatives have been done. For QSAR study, the 3D modeling and geometry optimization of all the derivatives and receptor's amino acid have been carried out on CAChe software by applying semiempirical method using MOPAC 2002. Softness Calculator using semiempirical PM3 methods has done the atomic softness of every atom of the derivatives and receptor's amino acids. The biological activities of tetrahydroimidazodiazepinone derivatives have been taken from the literature. The predicted values of biological activity with the help of multiple linear regression analysis are close to observed activity. The cross‐validation coefficient and correlation coefficient also indicate that the QSAR model is valuable. Regression analysis shows that hydrophobic interaction is predominant and made major contribution, whereas hydrogen bonding and polar interactions help in proper orientation of the compound (or its functional groups) to make maximum interaction. With the help of these descriptors, prediction of the biological activity of new derivative is possible. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009