Enoxacin as a second-generation synthetic quinolone is known for its antibacterial action; however, in recent years there have been studies focusing on its anticancer potential. Interestingly, it turns out that compared to other fluoroquinolones, enoxacin exhibits uncommon cytotoxic properties. Besides its influence on apoptosis, the cell cycle and cell growth, it exhibits a regulatory action on microRNA biogenesis. It was revealed that the molecular targets of the enoxacin-mediated inhibition of osteoclastogenesis are vacuolar H⁺-ATPase subunits and the c-Jun N-terminal kinase signaling pathway, causing a decrease in cell invasiveness. Interestingly, the prooxidative nature of the subjected fluoroquinolone enhanced the cytotoxic effect. Crucial for the anticancer activity were the carboxyl group at the third carbon atom, fluorine at the seventh carbon atom and nitrogen at the eighth position of naphyridine. Modifications of the parent drug improved the induction of oxidative stress, cell cycle arrest and the dysregulation of microRNA. The inhibition of V-ATPase–microfilament binding was also observed. Enoxacin strongly affected various cancer but not normal cells, excluding keratinocytes, which suffered from phototoxicity. It seems to be an underestimated anticancer drug with pleiotropic action. Furthermore, its usage as a safe antibiotic with well-known pharmacokinetics and selectivity will enhance the development of anticancer treatment strategies. This review covers articles published within the years 2000–2021, with a strong focus on the recent years (2016–2021). However, some canonical papers published in twentieth century are also mentioned.

Novel conjugates (CP) of moxifloxacin (MXF) with fatty acids (1m–16m) were synthesized with good yields utilizing amides chemistry. They exhibit a more pronounced cytotoxic potential than the parent drug. They were the most effective for prostate cancer cells with an IC₅₀ below 5 µM for respective conjugates with sorbic (2m), oleic (4m), 6-heptenoic (10m), linoleic (11m), caprylic (15m), and stearic (16m) acids. All derivatives were evaluated against a panel of standard and clinical bacterial strains, as well as towards mycobacteria. The highest activity towards standard isolates was observed for the acetic acid derivative 14m, followed by conjugates of unsaturated crotonic (1m) and sorbic (2m) acids. The activity of conjugates tested against an expanded panel of clinical coagulase-negative staphylococci showed that the compound (14m) was recognized as a leading structure with an MIC of 0.5 μg/mL denoted for all quinolone-susceptible isolates. In the group of CP derivatives, sorbic (2) and geranic (3) acid amides exhibited the highest bactericidal potential against clinical strains. The M. tuberculosis Spec. 210 strain was the most sensitive to sorbic (2m) conjugate and to conjugates with medium- and long-chain polyunsaturated acids. To establish the mechanism of antibacterial action, selected CP and MXF conjugates were examined in both topoisomerase IV decatenation assay and the DNA gyrase supercoiling assay, followed by suitable molecular docking studies.

Four new Cu(II) complexes with N,N-disubstituted thiourea ligands containing different imide moieties were designed and synthesized as potential anticancer agents. Structural variations include imide rings with four (Cu1) or five (Cu2) methyl groups, and isopropyl-bearing derivatives (Cu3 and Cu4) differing in the substituent position. Elemental analysis, attenuated total reflectance FT-IR and UV-Vis spectroscopy confirmed that the complexes consist of one Cu(II) center coordinated by two thiourea ligands via thiocarbonyl sulfur and deprotonated nitrogen atoms, adopting a square-planar geometry. The biological activity was evaluated against human cancer cell lines (HTB-140, A549, PC3, SW480, SW620) and normal keratinocytes (HaCaT). The MTT assay revealed moderate antiproliferative activities, with Cu1 showing the highest potency, whereas Cu3 and Cu4 exhibited the strongest induction of apoptosis, as confirmed by Annexin V-FITC/7-AAD analysis. Lactate dehydrogenase measurements indicated that membrane damage occurs predominantly at higher concentrations, representing a secondary event in cell death. Additionally, all complexes reduced interleukin-6 secretion in cancer cells, with Cu4 showing the most consistent effect. Structure–activity relationship analysis indicates that the number, nature, and position of the imide ring substituents influence the biological response profile without substantially altering antiproliferative potency. Overall, complex Cu4 exhibits the most balanced activity profile and represents a promising candidate for further investigation