Design, synthesis, and biological investigation of quinoline/ciprofloxacin hybrids as antimicrobial and anti-proliferative agents

Ciprofloxacin-Piperazine C-7 linked quinoline derivatives 6a–c and 8a–c were synthesized and investigated for their antibacterial, antifungal, and anti-proliferative activities. Ciprofloxacin-quinoline-4-yl-1,3,4 oxadiazoles 6a and 6b showed promising anticancer activity against SR- leukemia and UO-31 renal cancer cell lines. The hybrids 8a–c and compound 6b exhibited noticeable antifungal activities against C. Albicans ; 8a experienced the most potent antifungal activity compared to Itraconazole with MICs of 21.88 µg/mL and 11.22 µg/mL; respectively. Most of derivatives displayed better antibacterial activity than the parent ciprofloxacin against all the tested strains. Compound 6b was the most potent against the highly resistant Gram-negative K. pneumoniae with MIC 16.96 of µg/mL relative to the parent ciprofloxacin (MIC = 29.51 µg/mL). Docking studies of the tested hydrides in the active site of Topo IV enzyme of K. pneumoniae ( 5EIX ) and S. aureus gyrase ( 2XCT) indicate that they had stronger binding affinity in both enzymes than ciprofloxacin but have different binding interactions. The hybrid 6b could be considered a promising lead compound for finding new dual antibacterial/anticancer agents. Moreover, Compound 8a could be a lead for discovering new dual antibacterial/antifungal agents. Graphical abstract