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, H-1 NMR, C-13 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.