Abstract
A new series of quinoline derivatives 6-30 was identified as potent a-glucosidase inhibitors. These analogs exhibited inhibitory potentials (IC50 values) in the ranges between 2.60 and 102.12 mu M. Among the series, compounds 24 (2.60 +/- 0.01 mu M), 27 (2.60 +/- 0.01 mu M) and 20 (2.86 +/- 0.01 mu M) were found to be exceptionally potent (>14 times the standard) inhibitors of alpha-glucosidase when compared to the standard acarbose (IC50 = 38.25 +/- 0.12 mu M). Molecular docking studies on the two most active compounds 24 and 27 corroborated that compound 24 adopted a linear position to optimally fit into the binding site of a-glucosidase. Observations for the best position of compound 24 showed a total of four interactions towards catalytically active site residues of a-glucosidase involving amino acid residues such as Phe-177 and Asp-214. The oxadiazole ring of compound 24 interacted with His-279. Compound 27 formed one hydrogen bond interaction (N-methylacetamide) and three arene-arene interactions (quinoline and 1,3,4-oxadiazole moiety). The quinoline moiety of compound 27 formed two p-interactions with Phe-157. All compounds were tested for cytotoxicity, but none of them was found to be cytotoxic.