Novel Quinolone substituted 1,3,4-oxadiazole derivatives: Design, synthesis, antimicrobial and anti-inflammatory potential

Abstract A novel series of quinolone-substituted 1,3,4-oxadiazole derivatives 4(a-l) have been designed and synthesized. The target compounds were investigated for their antibacterial activity against gram positive (Staphylococcus aureus, ATCC 25923, Enterococcus faecalis, ATCC 29212) and gram negative bacterium (Escherichia coli, ATCC 25922, Pseudomonas aeruginosa, ATCC 27853) for antifungal activity using candida albicans (ATCC 10231) and anti-inflammatory activity as COX-II inhibitors, respectively. The 1,3,4-oxadiazole functionality was introduced at C-6 position of pipemidic acid derivatives. The structure of synthesized derivatives was confirmed by IR, 1H NMR and Mass spectrometry techniques. The quinolone (pipemidic acid)-oxadiazole hybrid derivatives were found to be effective against bacterial strains. When compared to ciprofloxacin (MIC 16 µg/mL), the compounds under consideration (4f, 4h, and 4k) showed potent antibacterial activity against all bacterial strains except Enterococcus faecalis, with MICs of 8 µg/mL. On the other hand, synthesized target compounds (4a–l) did not respond well against the Candida albicans fungal strain. The compound (4k) represents the high % inhibition against COX-II. The compounds (4f, 4h & 4k) exhibited the highest hydrogen bonding interaction with ARG57, ARG72, ARG78, LEU54 and MET16 target residues with a binding energy of -8.4, -8.6 & -8.5 kcal/mol into the active pocket of DNA gyrase enzyme respectively even better in comparison to reference ligands. Based on the docking study, the quinolone (pipemidic acid) oxadiazole hybrid structural ligands exhibited strong interaction at binding pockets of DNA gyrase enzyme.