Synthesis, in vitro, in silico, and molecular docking studies of some new benzothiazole-linked pyrazoline derivatives as orally administered beta-ketoacyl-ACP synthase III and malonyl-CoA inhibitors

Abstract

A new series of 2-[4-(1,3-benzothiazole-2-yl)phenoxy]-1(3-substituted-[5-substituted])-1H-pyrazole-1-yl) ethan-1-ones (9a-l) was synthesized by reacting 2-[4-(1,3-benzothiazol-2-yl)phenoxy]acetohydrazide (8) with different chalcones (3a-l). The antibacterial potential of the synthesized compounds was determined by established methods including determination of MIC and zone of inhibition. Although all the synthesized derivatives were found to possess good antibacterial activity against Gram (-ve) and Gram (+ve) bacterial strains, compounds 9e, 9i, 9j, and 9k were found to be better than the others. The data obtained through in silico studies bolstered the results of in vitro antibacterial studies and indicated that these compounds interacted with the N-terminal domain of β-ketoacyl-ACP Synthase III and malonyl-CoA Inhibitor (DNA binding protein, PDB ID: 1HNJ) through H-bond.. KEYWORDS :Antibacterial activity, β-Ketoacyl-ACP synthase III and malonyl-CoA, MIC value, Zone of inhibition.