Novel sulfonyl hydrazide based ß-carboline derivatives as potential α-glucosidase inhibitors: design, synthesis, and biological evaluation.

ABSTRACT

A series of novel sulfonyl hydrazide based ß-carboline derivatives (SX1-SX32) were designed and synthesized, and their structures were characterized on NMR and HRMS. Their α-glucosidase inhibitory screening results found that compounds (SX1-SX32) presented potential α-glucosidase inhibitory IC50 values being 2.12 ± 0.33-19.37 ± 1.49 µM. Compound SX29 with a para-phenyl (IC50 2.12 ± 0.33 µM) presented the strongest activity and was confirmed as a noncompetitive inhibitor. Fluorescence spectra, CD spectra and molecular docking were conducted to describe the inhibition mechanism of SX29 against α-glucosidase. Cells cytotoxicity indicated SX29 (0-32 µM) had no cytotoxicity on 293T cells. In particular, in vivo experiments revealed that oral administration of SX29 could regulate hyperglycemia and glucose tolerance of diabetic mice. These achieved findings indicated that sulfonyl hydrazide based ß-carboline derivatives bore promising potential for discovering new α-glucosidase inhibitors with hypoglycemic activity.