Design, synthesis and in vitro alpha-glucosidase inhibition of novel dihydropyrano[3,2-c]quinoline derivatives as potential anti-diabetic agents

A novel series of dihydropyrano[3,2-c]quinoline derivatives 6a-q were synthesized and evaluated for their in vitro alpha-glucosidase inhibitory activities. All newly synthesized compounds displayed potent alpha-glucosidase inhibitory activity in the range of 10.3 +/- 0.3 mu M-172.5 +/- 0.8 mu M against the yeast alpha-glucosidase enzyme when compared to the standard drug acarbose (IC50 = 750.0 +/- 1.5 mu M). Among these compounds, compounds 6e and 6d displayed the most potent alpha-glucosidase inhibitory activity (IC50 = 10.3 +/- 0.3 and 15.7 +/- 0.5 mu M, respectively). The kinetic analysis of the most potent compounds 6e and 6d revealed that compound 6e inhibited alpha-glucosidase in an uncompetitive manner (K-i = 11 mu M) while compound 6d was a non-competitive inhibitor (K-i = 28 mu M) of the enzyme. Then, the cytotoxicity of the most potent compounds (i.e., compounds 6a, 6d, 6e, 6 g, 6j, and 61) were evaluated for toxicity using the breast cancer cell lines MDA-MB231, MCF-7, and T-47D by using a MIT assay, and no toxicity was observed. (C) 2018 Elsevier Inc. All rights reserved.