QSAR, HQSAR AND DOCKING BASED DESIGNING OF PYRIDO [1, 2] A BENZIMIDAZOLE DERIVATIVES AS ANTI-MALARIAL AGENTS

Abstract

The docking and Quantitative structure-activity relationship (QSAR) studies of Pyrido [1, 2] a benzimidazoles nucleus were performed on a series of 40 analogues. The training set consisting of 32 molecules in Comparative Molecular Field (CoMFA), Comparative molecular similarity indices analysis (CoMSIA) and Hologram QSAR(HQSAR) models gives cross-validated r2 (q2) and (S.E) standard error of 0.613, 0.980 and 0.021 and conventional on MMFF 94 q2 0.785 r2 0.942 and (S.E) standard error 0.033 respectively. The predicted r2 values 0.882, 0.788 and 0.867 for Comparative Molecular Field Analysis (CoMFA) modeling, CoMSIA modeling and HQSAR modeling respectively, shows these generated models are appropriate for further designing. In addition to this work the docking studies were performed on Protein model of Plasmodium falciparum (PDB 2ANL) which further explore the binding affinity towards active site of protein receptor. The results guide us for the creation of more potent and effective compounds towards strain of Plasmodium falciparum relative to chloroquine.