Abstract

INSILICO STUDIES OF SOME NOVEL HETEROCYCLIC DERIVATIVES AS ANTICANCER AGENTS

G. Krishnamoorthy*, S. Shakila Banu, R. Senthamarai and A. M. Ismail

ABSTRACT

A set of eight substituted amino derivatives of 4-[(substituted amino)methyl]-N-(4-methyl-3-{[4-(1H-pyrrol-2-yl) pyrimidin-2-yl]amino}phenyl)benzamide were designed and screened for their physiochemical properties and druglikeliness score using Molinspiration software. All the newly designed compounds 13(a-h) were found in compliance with Lipinski’s rule of five recommendations for new chemical entities to have good oral bioavailability with no violations. All the compounds from 13(a-h) were further evaluated for their binding affinity towards Vascular Endothelial Growth Factor Receptor-2 which comprises the family of protein kinase and plays an important role in vascularization, growth and metastasis of tumor. Among the eight compounds 13(a-h), compounds 13f (-9.39 kcal/mol) and 13h (-9.09 kcal/mol) showed a better binding affinity compared to the standard drug sunitinib (-8.97kcal/mol). All the other compounds showed lesser binding energies compared to the standard. In order to conclude, compounds 13f and 13h can be selected as an efficient lead compound for further anticancer studies targeting protein kinase receptor.

Keywords: Pyrimidine, pyrrole, molinspiration, anticancer activity and docking.