Synthesis and biological evaluation of 2,5-disubstituted furan derivatives containing 1,3-thiazole moiety as potential α-glucosidase inhibitors

alpha-Glucosidase, which is involved in the hydrolysis of carbohydrates to glucose and directly mediates blood glucose elevation, is a crucial therapeutic target for type 2 diabetes. In this work, 2,5-disubstituted furan derivatives containing 1,3-thiazole-2-amino or 1,3-thiazole-2-thiol moiety (III-01 similar to III-30) were synthesized and screened for their inhibitory activity against alpha-glucosidase. alpha-Glucosidase inhibition assay demonstrated that all compounds had IC50 in the range of 0.645-94.033 mu M and more potent than standard inhibitor acarbose (IC50 = 452.243 +/- 54.142 mu M). The most promising inhibitors of the two series were compound III-10 (IC50 = 4.120 +/- 0.764 mu M) and III-24 (IC50 = 0.645 +/- 0.052 mu M), respectively. Kinetic study and molecular docking simulation revealed that compound III-10 (Ki = 2.04 +/- 0.72 mu M) is a competitive inhibitor and III-24 (Ki = 0.44 +/- 0.53 mu M) is a noncompetitive inhibitor against alpha-glucosidase. Significantly, these two compounds showed nontoxicity towards HEK293, RAW264.7 and HepG2 cells, suggesting that compounds may be considered as a class of potential candidates for further developing novel antidiabetic drugs.