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

Abstract

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