Synthesis, antitumor, antibacterial and urease inhibitory evaluation of new piperazinyl N-4 carbamoyl functionalized ciprofloxacin derivatives

Abstract

Background: Quinolones are well known antibacterial chemotherapeutics. Furthermore, they were reported for other activities such as anticancer and urease inhibitory potential. Modification at C7 of quinolones can direct these compounds preferentially toward target molecules.

Methods: Different derivatives of ciprofloxacin by functionalization at the piperazinyl N-4 position with arylidenehydrazinecarbonyl and saturated heterocyclic-carbonyl moieties have been synthesized and characterized using different spectral and analytical techniques. The synthesized compounds were evaluated for anticancer, antibacterial, and urease inhibitory activities.

Results: Among the synthesized compounds derivatives 3f and 3g experienced a potent antiproliferative activity against the breast cancer BT-549 cell line, recording growth percentages of 28.68% and 6.18%, respectively. Additionally, compound 3g revealed a remarkable antitumor potential toward the colon cancer HCT-116 cells (growth percentage 14.76%). Activity of compounds 3f and 3g against BT-549 cells was comparable to doxorubicin (IC₅₀ = 1.84, 9.83, and 1.29 µM, respectively). Test compounds were less active than their parent drug, ciprofloxacin toward Klebsiella pneumoniae and Proteus mirabilis. However, derivative 4a showed activity better than chloramphenicol against Klebsiella pneumoniae (MIC = 100.64 and 217.08 µM, respectively). Meanwhile, many of the synthesized compounds revealed a urease inhibitory activity greater than their parent. Compound 3i was the most potent urease inhibitor with IC₅₀ of 58.92 µM, greater than ciprofloxacin and standard inhibitor, thiourea (IC₅₀ = 94.32 and 78.89 µM, respectively).

Conclusion: This study provided promising derivatives as lead compounds for development of anticancer agents against breast and colon cancers, and others for optimization of urease inhibitors.

Keywords: Antibacterial; Anticancer; Carbamoyl; Ciprofloxacin; Molecular docking; Urease inhibitors.