N-Acylated Ciprofloxacin Derivatives: Synthesis and In Vitro Biological Evaluation as Antibacterial and Anticancer Agents.

A novel series of N-acylated ciprofloxacin (CP) conjugates were synthesized and screened as potential antimicrobial agents. Conjugates and were 1.25-10-fold more potent than CP toward all (minimal inhibitory concentration 0.05-0.4 μg/mL). Most of the chloro- (), bromo- (), and CF-alkanoyl () derivatives expressed higher or comparable activity to CP against selected Gram-positive strains. A few CP analogues (, , and ) were also more effective toward the chosen clinical Gram-negative rods. Conjugates , , and considerably influenced the phases of the bacterial growth cycle over 18 h. Additionally, compounds , , , and exerted stronger tuberculostatic action against three isolates than the first-line antitubercular drugs. Amides , , , , , and targeted gyrase and topoisomerase IV at 2.7-10.0 μg/mL, which suggests a mechanism of antibacterial action related to CP. These findings were confirmed by molecular docking studies. In addition, compounds and showed high antiproliferative activities against prostate PC3 cells (IC 2.02-4.8 μM), up to 6.5-2.75 stronger than cisplatin. They almost completely reduced the growth and proliferation rates in these cells, without a cytotoxic action against normal HaCaT cell lines. Furthermore, derivatives and induced apoptosis/necrosis in PC3 cells, probably by increasing the intracellular ROS amount, as well as they diminished the IL-6 level in tumor cells.