Exploiting oxadiazole-sulfonamide hybrids as new structural leads to combat diabetic complications via aldose reductase inhibition.

• Synthesis of a new series of oxadiazole-sulfonamide hybrids. • Derivatives exhibited the significant inhibition pattern towards aldose reductase. • Few compounds were active against aldehyde reductase. • Moreover, the cytotoxic profile of the newly synthesized compounds was checked. • Molecular docking and MD simulations were performed. A series of oxadiazole-sulfonamide hybrids was synthesized through multistep reaction and for the formation of targeted thioethers 6 (a-l), a much facile route was adopted through which S-alkylation was successfully carried out at room temperature. These novel thioethers 6 (a-l) were later screened against aldehyde reductase (ALR1) and aldose reductase (ALR2). Beside the enzyme inhibition studies, the compounds were also tested against cervical cancer cell lines (HeLa). The results suggested the significant inhibition pattern towards ALR2, while few compounds were active against ALR1. The synthesized derivatives have shown weak to moderate cytotoxicity. The most potent inhibitors (6b , 6e , 6f and 6l) were selected for molecular docking studies and the binding interactions were reported. [ABSTRACT FROM AUTHOR]

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