CoMFA and CoMSIA Analysis of Tetrahydroquinolines as Potential Antimalarial Agents

Abstract

The CoMFA and CoMSIA studies have been carried out on a dataset of compounds some of which have been reported to inhibit Plasmodium falciparum protein farnesyltransferase. The co-crystal structure of lead molecule BMS-214662 bound to Rat PFT was used as a template for the investigation. The CoMFA has led to good model with r2ncv=0.909, r2cv=0.617 and validated with external set (r2pred=0.748) when compared to that of CoMSIA. In CoMFA model the steric and electrostatic fields have exerted almost equal influence on the activity. The contour maps have indicated the necessity of sterically large electropositive groups with electronegative tail and sterically large electronegative moieties on the sulfonamide linker present in these molecules for activity. Incorporating these features some new compounds are identified for further investigation.