Design, synthesis, and biological evaluation of novel ciprofloxacin derivatives as potential anticancer agents targeting topoisomerase II enzyme

A series of novel ciprofloxacin (CP) derivatives substituted at the N-4 position with biologically active moieties were designed and synthesised. 14 compounds were 1.02- to 8.66-fold more potent than doxorubicin against T-24 cancer cells. Ten compounds were 1.2- to 7.1-fold more potent than doxorubi...

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Bibliographic Details
Published in:Journal of enzyme inhibition and medicinal chemistry 2023-12, Vol.38 (1), p.118-137
Main Authors: Swedan, Hadeer K., Kassab, Asmaa E., Gedawy, Ehab M., Elmeligie, Salwa E.
Format: Article
Language:English
Subjects:
anti-proliferative activity
Antineoplastic Agents - chemistry
Antineoplastic drugs
Antitumor agents
Apoptosis
Biological activity
Cancer
Caspase-3
Cell cycle
Cell Line, Tumor
Cell Proliferation
Ciprofloxacin
Ciprofloxacin - chemistry
Ciprofloxacin - pharmacology
Design
DNA topoisomerase (ATP-hydrolysing)
DNA Topoisomerases, Type II - metabolism
Dose-Response Relationship, Drug
Doxorubicin
Doxorubicin - pharmacology
Drug Screening Assays, Antitumor
G1 phase
Molecular Docking Simulation
Molecular Structure
Research Paper
S phase
Structure-Activity Relationship
synthesis
topoisomerase II
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Summary:A series of novel ciprofloxacin (CP) derivatives substituted at the N-4 position with biologically active moieties were designed and synthesised. 14 compounds were 1.02- to 8.66-fold more potent than doxorubicin against T-24 cancer cells. Ten compounds were 1.2- to 7.1-fold more potent than doxorubicin against PC-3 cancer cells. The most potent compounds 6, 7a, 7b, 8a, 9a, and 10c showed significant Topo II inhibitory activity (83-90% at 100 μM concentration). Compounds 6, 8a, and 10c were 1.01- to 2.32-fold more potent than doxorubicin. Compounds 6 and 8a induced apoptosis in T-24 (16.8- and 20.1-fold, respectively compared to control). This evidence was supported by an increase in the level of apoptotic caspase-3 (5.23- and 7.6-fold, sequentially). Both compounds arrested the cell cycle in the S phase in T-24 cancer cells while in PC-3 cancer cells the two compounds arrested the cell cycle in the G1 phase. Molecular docking simulations of compounds 6 and 8a into the Topo II active site rationalised their remarkable Topo II inhibitory activity.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2022.2136172