Probing 2-acetylbenzofuran hydrazones and their metal complexes as α-glucosidase inhibitors

Abstract

Inhibition of α-glucosidase is one of the important approaches in designing antidiabetic drugs for its role in decrease of the carbohydrates digestion to avoid post-prandial increase in blood sugar levels in diabetic patients. In the present study we designed a novel series of 2-acetylbenzofuran hydrazones (L1-L7) and their metal (II) complexes Cu (II), Co (II), Zn (II) and Mn (II) (8-29) and screened for inhibitory activity against the yeast α-glucosidase. The synthesis of hydrazones incorporated the use of I₂ as a catalyst which resulted in excellent yield of 94%. The ligand L3, showed good activity (IC₅₀ = 47.51 ± 0.86 µM) while its metal complex (10) showed potent activity (IC₅₀ = 1.15 ± 0.001 µM) compared to reference acarbose IC₅₀ = 378.25 ± 0.12 µM. Similarly, the Cu (II) complexes with ligands L5 and L6 showed excellent α-glucosidase inhibition (IC₅₀ = 0.15 ± 0.003 12 and 0.21 ± 0.002 µM for 13, respectively) whereas, the metal complexes of Co (II), Mn (II), and Zn (II) showed moderate to poor inhibitory activities against α-glucosidase. The The findings are supported by the ligands and enzyme interactions through molecular docking studies. In conclusion, it is indicated that metal complexes of 2-acetylbenzofuran hydrazones have good potential for research leading to antidiabetic therapies.

Keywords: Acetylbenzofuran; Hydrazones; Metal complexes; α-glucosidase inhibitors.