Synthesis, in vitro biological analysis and molecular docking studies of new thiadiazole-based thiourea derivatives as dual inhibitors of a-amylase and a-glucosidase

Abstract

Diabetes mellitus is a syndrome that is caused due to the imbalance of insulin production in the body. In the present study we have synthesized a class of fifteen compounds (1–15) based on thiadiazole-bearing thiourea that were assessed for in vitro alpha-amylase and alpha-glucosidase inhibitory potentials against standard drug acarbose. In this series, all the synthesized scaffolds were recognized as potentials inhibitors of both targeted enzymes, α-amylase having varied range from IC50 values = 35.70 ± 0.70 µM to 1.30 ± 0.05 µM against standard drug acarbose (10.30 ± 0.20 µM) while for α-glucosidase IC50 values = 37.60 ± 0.80 µM to 2.20 ± 0.10 µM against standard drug acarbose (9.80 ± 0.20 µM). Among the series, nine scaffolds such as 4, 6, 7, 9, 8, 11, 12, 14 and 15 showed excellent activity against a-amylase and a-glucosidase and were found many folds more potent than standard acarbose drugs due to the change in nature and number/s of substituent along the entire skeleton. A molecular docking study was conducted against active compounds to understand the binding modes of the synthetic analogs and how they show interaction with the active part of the enzymes. To confirm the structure of synthetic analogs different spectroscopic techniques will be used like NMR and HREI-MS.

Keywords

• Thiadiazole
• Thiourea
• α-amylase
• α-glucosidase
• SAR and Docking study