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

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.

Design, modification of phyllanthone derivatives as anti-diabetic and cytotoxic agents.

Twelve benzylidene derivatives, one Baeyer-Villiger oxidative, six imine derivatives were successfully designed and synthesised from phyllanthone. In the search for potential new anti-diabetic agents, phyllanthone along with its benzylidene and oxidation analogues were evaluated for enzyme inhibition against α-glucosidase. In the benzylidene series, most analogues displayed stronger activity than the mother compound. Compound 1c revealed the strongest activity, outperforming the acarbose positive control with an IC50 value of 19.59 µM. Phyllanthone and its derivatives were then tested for cytotoxic activity against the K562 cell line. The imine analogues displayed the most powerful cytotoxic activity with 3cand 3d having IC50 values of 57.55 and 68.02 µM, respectively.