New carbazole linked 1,2,3-triazoles as highly potent non-sugar α-glucosidase inhibitors

Abstract

In the present study, a series of new carbazole linked 1H-1,2,3-triazoles (2-27) were synthesized via click reaction of N-propargyl-9H-carbazole (1) and azides of appropriate acetophenones and heterocycles. Synthesized carbazole triazoles including 7, 9, 10, 19, 20, and 23-26 (IC₅₀=0.8±0.01-100.8±3.6μM), exhibited several folds more potent α-glucosidase inhibitory in vitro activity as compared to standard drug, acarbose. Compounds 2-5, 7-13, and 17-27 did not show any cytotoxicity against 3T3 cell lines, except triazoles 6, and 14-16. Among the series, carbazole triazoles 23 (IC₅₀=1.0±0.057μM) and 25 (IC₅₀=0.8±0.01μM) were found to be most active, and could serve as an attractive building block in the search of new non-sugar derivatives as anti-diabetic agents.

Keywords: Acetophenones; Carbazole; Click chemistry; Diabetes; Triazoles; α-Glucosidase.