A novel series of N-acylated ciprofloxacin (CP) conjugates1–21were synthesized and screened as potential antimicrobial
agents. Conjugates1and2were 1.25–10-fold
more potent than CP toward allStaphylococci(minimal inhibitory concentration 0.05–0.4 μg/mL).
Most of the chloro- (3–7), bromo- (8–11), and CF3-alkanoyl (14–16) derivatives
expressed higher or comparable activity to CP against selected Gram-positive
strains. A few CP analogues (5,10, and11) were also more effective toward the chosen clinical Gram-negative
rods. Conjugates5,10, and11considerably influenced the phases of the bacterial growth cycle
over 18 h. Additionally, compounds2,4–7,9–12, and21exerted stronger
tuberculostatic action against threeMycobacterium
tuberculosisisolates than the first-line antitubercular
drugs. Amides1,2,5,6,10, and11targeted 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, compounds3and15showed high antiproliferative activities
against prostate PC3 cells (IC502.02–4.8 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, derivatives3and21induced apoptosis/necrosis in PC3 cells,
probably by increasing the intracellular ROS amount, as well as they
diminished the IL-6 level in tumor cells.