Antimalarial evaluation and docking studies of hybrid phenylthiazolyl-1,3,5-triazine derivatives: A novel and potential antifolate lead for Pf-DHFR-TS inhibition

Present communication deals with the docking study of hybrid phenyl thiazolyl-1,3,5-triazine analogues (1a-36d) on three selected different binding site viz., alpha, beta and gamma of wild type Pf-DFHR-TS. In admiration of excellent H-bond scoring, with regard to cycloguanil and to a large extent similar scoring with WR99210, compound 4a, 12b, 21c, 23c, 28d, 29d, 34d, and 35d were selected for in vitro antimalarial activity against 3D7 strain of Plasmodium falciparum. Findings from the study disclose that a significant correlation was exist between in vitro results and in silico prediction (r(2) = 0.543). Furthermore, investigation of structure-activity relationships elucidate crucial structural requirement for site specific binding of ligands. (C) 2012 Elsevier Inc. All rights reserved.