Structural modification of tanshinone IIA and their α-glucosidase inhibitory activity

Abstract

α-Glucosidase is one of the therapeutic approaches for treating type 2 diabetes mellitus. Almost 95 % of diabetes patients worldwide have been diagnosed with type 2 diabetes, resulting in 1.5 million fatalities each year. Newly synthesized oxazole-based tanshinone IIA derivatives (1a-n) were designed and evaluated for their inhibitory activity against α-glucosidase enzyme. Eight compounds (1a-d, 1f-g, 1j, and 1m) demonstrated excellent inhibition with IC₅₀ values ranging from 0.73 ± 0.11 to 9.46 ± 0.57 μM as compared to tanshinone IIA (IC₅₀ = 11.39 ± 0.77 μM) and standard acarbose (IC₅₀ = 100.00 ± 0.95 μM). Among this series, 1j bearing two hydroxyls group over the phenyl ring was identified as the most potent α-glucosidase inhibitor with IC₅₀ value of 0.73 ± 0.11 μM. Molecular docking simulations were done for the most active compound to identify important binding modes responsible for inhibition activity of α-glucosidase. In addition, the kinetic study was also performed to understand the mode of inhibition.

Keywords: Diabetes; Oxazole; Tanshinone IIA; α-Glucosidase inhibitor.