Anticancer Activity of Fluoroquinolone Derivatives

Fluoroquinolones, a class of broad-spectrum antibacterial agents, have emerged as a versatile scaffold for the development of anticancer compounds. Structural modification of the core 4-quinolone-3-carboxylic acid framework—particularly at the C-7 and C-3 positions—yields derivatives that interfere with eukaryotic topoisomerase I and II, induce cell-cycle arrest and trigger apoptosis. These compounds display activity against a range of malignancies, including breast, colon, pancreatic, melanoma and bladder cancers. Mechanistic studies reveal that selected analogues promote DNA damage via topoisomerase poisoning, disrupt tubulin polymerisation, elevate reactive oxygen species and suppress pro-inflammatory cytokines. Many derivatives also exhibit the capacity to overcome multidrug resistance and synergise with established chemotherapeutics, offering improved selectivity and reduced systemic toxicity. Advances in structure–activity relationships have guided the optimisation of cell permeability, target affinity and pharmacokinetic profiles. The repositioning of fluoroquinolones leverages their known safety record, enabling accelerated preclinical evaluation. Collectively, this body of work underscores the global significance of fluoroquinolone derivatives as small-molecule leads in anticancer drug discovery.

Research from Nature Portfolio

Recent studies have described the synthesis of new cytotoxic fluoroquinolone analogues by functionalising the hydrazide derivatives of moxifloxacin, ofloxacin and ciprofloxacin. Lead compounds exhibited sub-micromolar GI50 values across a panel of tumour cell lines, notably breast, lung and central nervous system models. These analogues arrested cancer cells at G1/S or G1, depending on substituent pattern, and activated intrinsic apoptotic pathways as evidenced by increased Bax/Bcl-2 ratios and caspase-9 cleavage. Preferential inhibition of topoisomerase II over type I was confirmed both biochemically and by molecular docking, which revealed distinct binding modes compared with classical poisons. In silico absorption, distribution, metabolism and excretion (ADME) predictions indicated high oral bioavailability, low central nervous system penetration and minimal plasma-protein binding, highlighting these derivatives as promising leads for further optimisation.

Anticancer Activity of Fluoroquinolone Derivatives publication trend

The graph below shows the total number of articles in anticancer activity of fluoroquinolone derivatives across all publications each year (not limited to Nature Index journals).

Technical terms

Topoisomerase I/II: Enzymes that relieve DNA supercoiling by transiently cleaving and rejoining DNA strands.

Apoptosis: Programmed cell death involving a cascade of regulated molecular events.

Cell-cycle arrest: Halting of cell-division progression at specific checkpoints (e.g., G1/S, G2/M).

GI50: Concentration of compound required to inhibit cell growth by 50%.

Hybrid molecule: Compound combining two distinct pharmacophoric units to enhance activity or selectivity.

References

1. Advancements in Synthetic Strategies and Biological Effects of Ciprofloxacin Derivatives: A Review. International Journal of Molecular Sciences (2024).
2. Unveiling the Anticancer Potential of a New Ciprofloxacin-Chalcone Hybrid as an Inhibitor of Topoisomerases I & II and Apoptotic Inducer. Molecules (2024).
3. Design and synthesis of novel cytotoxic fluoroquinolone analogs through topoisomerase inhibition, cell cycle arrest, and apoptosis. Scientific Reports (2023).