Imidazole‐Oxadiazole Hybrid as Potential Antimicrobial Agents: Design, Synthesis, Drug–Likeness, Pharmacophore and Molecular Docking Study

A new series of imidazole linked 1,3,4‐oxadizoles were designed and synthesized from 2‐butyl‐4‐chloro‐1H‐imidazole‐5‐carbaldehyde (1) as a starting material. The synthesized compounds were characterized by well–known spectroscopic techniques, i. e., IR, 1H NMR, 13C NMR, and mass spectrometry. Against Gram–positive bacteria S. aureus, compounds 8 e, 8 i, and 8 k showed the highest antibacterial activity with diameter zone values 25±0.44, 25±0.65, 22±0.91 mm respectively. Compounds 8 e, 8 g, and 8 i are active against Gram–negative bacteria E. coli with ZI of 26±0.58, 21±0.51, 26±0.71 mm. Interestingly, the molecules 8 a, and 8 h were more selective towards antifungal activity against F. oxysporum (ZI=21±0.11, 21±0.51 mm), compared to clotrimazole (19±0.13 mm). The docking study results of compound 8 d formed highly stable H‐bonding with Asp‐89, Asn‐145, Val‐88, Arg‐144 amino acids, which are plays a crucial role in ensuring efficient binding of the ligand in a crystal structure of S. aureus mutated in GyrB ATPase domain (PDB: 3U2K). The study of computer aided ADMET was also carried out, using SwissADME, ADMETlab2.0 to investigate the pharmacokinetic properties of the tested triazole compounds. A new series of DNA gyrase inhibitors with Imidazole‐oxadiazole were designed, and synthesized. Among the synthesized compounds, compounds 8 d and 8 i exhibited strong antimicrobial activity against standard drug ciprofloxacin and fluconazole. To understand the mechanism of binding interactions between the 1,3,4‐oxadiazoles and the crystallographic GyrB ATPase domain in the S. aureus receptor, molecular docking, in silico ADME, and toxicity studies were carried out.