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Abstract

A novel series of amide analogs of p-thymol, clubbed with 1,3,4-thiadiazole (8a-8l) was developed and synthesized. This was achieved by attaching the phenolic group of the naturally occurring p-thymol core to 1,3,4-thiadiazole, followed by coupling with various substituted acyl chloride moieties through an amino linker, resulting in a good yield (83-91 %). The identities of all the synthesized compounds were confirmed using spectroscopic methods, including 1H NMR, 13C NMR, mass spectrometry, and FT-IR. In this study, the biological activity profile of the designed analogs was predicted using the PASS prediction tool, indicating their potential antidiabetic activity. The compounds were synthesized, and their activities were experimentally assessed at a concentration of 62.5 500 µL. The observed experimental activity was aligned with the predictions made by PASS. Molecular docking studies were conducted to determine the binding free energies of all the compounds at the active site of isomaltase from S. cerevisiae (PDB ID: 3A47). Compounds 8a and 8d exhibited excellent docking scores. The synthesized compounds were evaluated for their in vitro antidiabetic activity and showed moderate-to-good results. Notably, compounds 8a, 8e, 8j, and 8l exhibited significant antidiabetic activity compared with the positive standard acarbose. A comparative analysis of Lipinski’s parameters and compound activity showed that all compounds adhered to Lipinski’s rule of five.