Synthesis, Antibacterial Evaluation and Molecular Docking Studies of 1,3,4‐Oxadiazole‐2(3H)‐Thione‐Norfloxacin Hybrids as Potent Antibacterial Agents

Abstract

Novel 1,3,4‐oxadiazole‐2(3H)‐thione‐norfloxacin hybrids were rationally designed based on the pharmacophore hybridization concept and yielded ten potent hybrids. All attained compounds were characterized applying electrospray ionization‐mass spectrometry, nuclear magnetic resonance, and Fourier‐transform infrared spectrophotometry. Compounds 3 c and 3 g were also characterized by single‐crystal X‐ray diffraction techniques. In vitro antibacterial activity of the attained hybrids was evaluated against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. All hybrids exhibited potent antibacterial activity against the test strains with MIC values between ≤0.125 and 1 μg/mL, which were more potent than the parent drug norfloxacin against P. aeruginosa. In particular, compounds 3 a, 3 e, and 3 f were more potent against S. aureus. The hybrid 3 e, with the smallest MIC and MBC against the test strains, showed rapid bactericidal activity in the time‐kill assays and eliminated S. aureus and E. coli <2 h of treatment. Meanwhile, cytotoxicity and hemolysis assays revealed low toxicity of the synthesized hybrids. Molecular docking studies indicated an improved receptor‐hybrid affinity towards DNA topoisomerase IV, showing a least binding energy of −9.4 to −10.0 kcal/mol. Among all the synthesized hybrids, 3 e can be a potential candidate for further antibiotic development.

In vitro and In silico Evaluation of Antibacterial Effects in Some Oxadiazole Compounds against Escherichia coli O157: H7

“…In a related study, Luo et al conducted antibacterial evaluation and molecular docking studies of 1,3,4-Oxadiazole-2(3H)-Thione-norfloxacin hybrids as potent antibacterial agents and reported an enhanced receptor-hybrid affinity towards DNA topoisomerase IV, with a minimum binding energy of -9.4 to -10.0 kcal/mol. Among all the synthesized hybrids, 3e could be a potential candidate for further antibiotic development (30).…”