Synthesis of benzimidazole-thiosemicarbazone hybrid derivatives, in vitro ..-glucosidase and ..-amylase activities, and an in silico molecular docking study

We synthesised fourteen benzimidazole-thiosemicarbazone hybrid compounds (1–14) as α-glucosidase and α-amylase inhibitors and examined them using various spectroscopic methods. All analogs were determined to be active and had IC50 values ranging from 3.20 ± 0.20 to 37.40 ± 0.20 µM (α-glucosidase) and 1.30 ± 0.10 to 19.30 ± 0.10 µM (α-amylase) when compared to reference drug acarbose (IC50 = 38.45 ± 0.80 & 11.12 ± 0.15 µM, respectively). Analogs 4 and 6 in both cases were able to survive the first and second most potent analogues in the series with IC50 values of 3.20 ± 0.30 & 1.30 ± 0.10 µM and 6.20 ± 0.10 & 3.10 ± 0.20 µM, respectively. The type, number, and position of substitution on the phenyl ring were found to be primary determinants of structure–activity relationship. A molecular docking study was done to determine how the most potent analogues interacted with the active sites of amino acids.