Imidazole‐Oxadiazole Hybrid as Potential Antimicrobial Agents: Design, Synthesis, Drug–Likeness, Pharmacophore and Molecular Docking Study
Anjanareddy Basava Reddy, Tejeswara Rao Allaka, Vidya Sagar Reddy Avuthu, Pilli V.V.N. Kishore, H. Nagarajaiah
Abstract
Abstract A new series of imidazole linked 1,3,4‐oxadizoles were designed and synthesized from 2‐butyl‐4‐chloro‐1 H ‐imidazole‐5‐carbaldehyde ( 1 ) as a starting material. The synthesized compounds were characterized by well–known spectroscopic techniques, i. e ., IR, 1 H NMR, 13 C 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.