Synthesis, biological evaluation and molecular modelling of 3-Formyl-6-isopropylchromone derived thiosemicarbazones as a-glucosidase inhibitors

Type-2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders in the world and over the past three decades its incidence has increased drastically. alpha-Glucosidase inhibitors are used to control the hyperglycemic affect of T2DM. Herein, we report the synthesis, alpha-glucosidase inhibition, structure activity relationship, pharmacokinetics and docking analysis of various novel chromone based thiosemicarbazones 3(a-r). The derivatives displayed potent activity against alpha-glucosidase with IC50 in range of 0.11 +/- 0.01-79.37 +/- 0.71 mu M. Among all the synthesized compounds, 3a (IC50 = 0.17 +/- 0.026 mu M), 3 g (IC50 = 0.11 +/- 0.01 mu M), 3n (IC50 = 0.55 +/- 0.02 mu M), and 3p (IC50 = 0.43 +/- 0.025 mu M) displayed higher inhibitory activity as compared to the standard, acarbose. Moreover, we have developed a statistically significant 2D-QSAR model (R-tr(2):0.9693; F: 50.4647 and Q(LOO)(2):0.9190), which can be used in future to further design potent thiosemicarbazones as inhibitors of alpha-glucosidase.

Automated summary

In this study, the synthesis, alpha-glucosidase inhibition, structure activity relationship, pharmacokinetics, and docking analysis of novel chromone-based thiosemicarbazones were reported. The derivatives exhibited potent activity against alpha-glucosidase, with certain compounds showing higher inhibitory activity than the standard acarbose. Moreover, a statistically significant 2D-QSAR model was developed for further design of potent thiosemicarbazones as alpha-glucosidase inhibitors.