Synthesis and molecular docking of new N4-piperazinyl ciprofloxacin hybrids as antimicrobial DNA gyrase inhibitors

Abstract

A series of N-4 piperazinyl ciprofloxacin derivatives as urea-tethered ciprofloxacin-chalcone hybrids 2a-j and thioacetyl-linked ciprofloxacin-pyrimidine hybrids 5a-i were synthesized. The target compounds were investigated for their antibacterial activity against S. aureus, P. aeruginosa, E. coli, and C. albicans strains, respectively. Ciprofloxacin derivatives 2a-j and 5a-i revealed broad antibacterial activity against either Gram positive or Gram negative strains, with MIC range of 0.06–42.23 µg/mL compared to ciprofloxacin with an MIC range of 0.15–3.25 µg/mL. Among the tested compounds, hybrids 2b, 2c, 5a, 5b, 5h, and 5i exhibited remarkable antibacterial activity with MIC range of 0.06–1.53 µg/mL against the tested bacterial strains. On the other hand, compounds 2c, 2e, 5c, and 5e showed comparable antifungal activity to ketoconazole against candida albicans with MIC range of 2.03–3.89 µg/mL and 2.6 µg/mL, respectively. Further investigations showed that some ciprofloxacin hybrids have inhibitory activity against DNA gyrase as potential molecular target compared to ciprofloxacin with IC50 range of 0.231 ± 0.01–7.592 ± 0.40 µM and 0.323 ± 0.02 µM, respectively. Docking studies of compounds 2b, 2c, 5b, 5c, 5e, 5h, and 5i on the active site of DNA gyrase (PDB: 2XCT) confirmed their ability to form stable complex with the target enzyme like that of ciprofloxacin. Graphical abstract

The Assessment of cytotoxicity, apoptosis inducing activity and molecular docking of a new ciprofloxacin derivative in human leukemic cells

“…The uoroquinolone of the second generation, cipro oxacin, is e cient against Pseudomonas aeruginosa and other gram-negative bacteria. The medication is widely available and has a good bioavailability [9][10][11]. Because of its favorable pharmacokinetic characteristics and capacity to accumulate in higher quantities in tissues than in plasma, cipro oxacin is frequently used to treat respiratory, urinary, and gastrointestinal infections [12].…”

Identification of Potential DNA Gyrase Inhibitors: Virtual Screening, Extra-Precision Docking and Molecular Dynamics Simulation Study

“…Hasan et al ., have carried out in silico analysis of ciprofloxacin derivatives as potential DNA gyrase inhibitors (Hasan et al, 2021). Mohammed et al ., have synthesized and performed docking studies of a few novel N4-piperazinyl ciprofloxacin analogues as potential DNA gyrase inhibitors (Mohammed et al, 2022). We wanted to identify some novel chemotypes which already might have antimicrobial activity, and be developed as DNA gyrase inhibitors.…”