Benzenesulfonamide based 1,3,4-oxadiazole derivatives: synthesis, pharmacokinetic property prediction, bovine carbonic anhydrase activity and molecular docking studies

Abstract

Sulphur-containing compounds are highly significant as they can possess a variety of biological activities that make them useful for pharmacological purposes and for the mechanism by which drugs such as antibiotics bind to and disrupt bacterial cell walls. In this study, novel thioalkyl substituted-1,3,4 oxadiazole-bearing sulfonamide compounds have been successfully synthesized and characterized by (HNMR)-H-1, (CNMR)-C-13, IR and elemental analysis. The effects of different thioalkyl groups on the 1,3,4 oxadiazole group, the IC(5)0 value for Bovine Carbonic Anhydrase (BCA) found by in vitro, density functional theory (DFT) calculations, pharmacokinetics prediction and molecular docking are aimed to reveal the interactions on BCA. Firstly, pharmacokinetic predictions of thioalkyl substituted 1,3,4-oxadiazole compounds were generated to predict their potential hazards. Secondly, the predicted molecular docking data and 2D interaction were analyzed based on the best configuration from DFT optimization. Finally, the inhibition against BCA was analyzed in vitro and compared with the theoretical data. The compound (5o) has the best value such as IC50 = 51.80 mu M, HOMO-LUMO (Delta E 4.488 Ev), Delta G -7.69 kcal/mol, Full fitness -2152.72 FF and predicted toxicity results showed no significant results except hepatotoxicity. [GRAPHICAL ABSTRACT]