Coumarin-Based Thiosemicarbazones: Synthesis, α-Amylase Inhibition and ADMET Analysis

Coumarin derivatives show various pharmaceutical properties, including anti-cancer, anti-bacterial, anti-coagulant, and anti-diabetic. A novel series of coumarin-thiosemicarbazone hybrids was prepared and characterized by using ¹HNMR, mass and IR spectroscopy. The prepared compounds were assessed for their in vitro α-amylase inhibitory activity. Among the screened hybrids, Compounds 3c (IC50= 10.58 ± 0.14 µM) and 3e (IC50= 9.41 ± 0.15 µM) showed excellent inhibition against α-amylase as compared to the reference drug (acarbose IC50= 16.38 ± 0.17 µM). Molecular docking study indicated that compounds 3c and 3e displayed the highest binding scores of -9.2 and -9.3 kcal/mol, respectively, towards the active sites of human pancreatic α-amylase (PDB ID: 2QV4). The acarbose had a binding score of -8.1 kcal/mol. Furthermore, ADMET analysis displayed that these potent derivatives exhibited high oral absorption, compliance with Lipinski’s rule, low toxicity predictions, and a promising overall drug-likeness.

Muhammad Shahid Nazir, Matloob Ahmad, Azhar Rasul