Discovering the anti-diabetic potential of thiosemicarbazone derivatives: In vitro α-glucosidase, α-amylase inhibitory activities with molecular docking and DFT investigations.

• Various para-substituted thiosemicarbazone derivatives have been successfully synthesized. • These derivatives were subjected for their anti-diabetic potential using α-glucosidase and α-amylase assays. • Molecular docking studies have been carried out to know the interactions between the compounds and the enzymes. • The chemical nature of these product compounds were determined through DFT studies. This work describes the synthesis of para -substituted thiosemicarbazone derivatives by refluxing 4-ethoxybenzaldehyde (1) and 4-nitrobenzaldehyde (2) with thiosemicarbazide in ethanol with acetic acid catalyst. The resultant thiosemicarbazones were then treated with various phenacyl bromides to get the product compounds. 1H NMR and EI-MS spectroscopic methods were employed to confirm the structures of these derivatives and screened the compounds for their in vitro α-glucosidase and α-amylase inhibitory activities. Six compounds (4e, 3e, 3c, 3b, 4b, and 4c) exhibited highest α-glucosidase activity in the range of IC 50 values of 2.81 ± 1.92 to 16.16 ± 0.15 µM. Similar to this, five compounds (3e, 4e, 3b, 3c, and 4c) attributed excellent inhibitory activity in the range of IC 50 values from 3.12 ± 0.13 to 16.56 ± 0.17 µM against the α-amylase enzyme when compare with the standard acarbose. The density functional theory (DFT) study demonstrated the stability, bioactivity, and charge transfer of the compounds, while the molecular docking analysis has provided significant understanding of how the compounds interact with the enzymes. These findings provide prospective directions for the development of innovative therapeutic candidates to regulate postprandial glucose levels in diabetic patients. [Display omitted] [ABSTRACT FROM AUTHOR]

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