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

Abstract

A novel series of N-acylated ciprofloxacin (CP) conjugates 1–21 were synthesized and screened as potential antimicrobial agents. Conjugates 1 and 2 were 1.25–10-fold more potent than CP toward all Staphylococci (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, and 11) were also more effective toward the chosen clinical Gram-negative rods. Conjugates 5, 10, and 11 considerably influenced the phases of the bacterial growth cycle over 18 h. Additionally, compounds 2, 4–7, 9–12, and 21 exerted stronger tuberculostatic action against three Mycobacterium tuberculosis isolates than the first-line antitubercular drugs. Amides 1, 2, 5, 6, 10, and 11 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 3 and 15 showed high antiproliferative activities against prostate PC3 cells (IC50 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 3 and 21 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.

Designing, Characterization, DFT, Biological Effectiveness, and Molecular Docking Analysis of Novel Fe(III), Co(II), and Cu(II) Complexes Based on 4-Hydroxy-2H-pyrano[3,2-c]quinoline-2,5(6H)-dione

“…Ciprofloxacin was used as the standard for biological application as it is used to treat various bacterial infections, such as those affecting the skin, lungs, bones, joints, urinary tract, and gastrointestinal tract. It can also be used to prevent or treat anthrax and plague exposure . Also, it has a broad spectrum of effectiveness against many types of bacteria, having Gram-positive and Gram-negative bacteria, anaerobes, and some atypical bacteria .…”

“…It can also be used to prevent or treat anthrax and plague exposure . Also, it has a broad spectrum of effectiveness against many types of bacteria, having Gram-positive and Gram-negative bacteria, anaerobes, and some atypical bacteria . Ciprofloxacin may be preferred over other antibiotic drugs for biological applications because of its high potency, low resistance rate, good tissue penetration, and oral availability …”

“…20 Also, it has a broad spectrum of effectiveness against many types of bacteria, having Gram-positive and Gram-negative bacteria, anaerobes, and some atypical bacteria. 20 Ciprofloxacin may be preferred over other antibiotic drugs for biological applications because of its high potency, low resistance rate, good tissue penetration, and oral availability. 20 The minimum inhibitory concentration (MIC, μM) can be defined as the lowest substance concentration, which stops detectable in vitro growth of bacteria or fungi.…”

“…20 Ciprofloxacin may be preferred over other antibiotic drugs for biological applications because of its high potency, low resistance rate, good tissue penetration, and oral availability. 20 The minimum inhibitory concentration (MIC, μM) can be defined as the lowest substance concentration, which stops detectable in vitro growth of bacteria or fungi. The MIC was calculated by testing a range of descending concentration, down to 10 μM, and utilizing the lowest concentration at which no inhibition activity was seen as the MIC, μM.…”

Novel Tetracyclic Azaphenothiazines with the Quinoline Ring as New Anticancer and Antibacterial Derivatives of Chlorpromazine

“…Additional details regarding the conducted biological studies, including cell culture, appropriate conditions, and methodology, were provided in our previous publication [66].…”