Anticancer Effect of the Triphenylphosphonium-Conjugated Quinolone Antibiotics Targeting Mitochondrial DNA Replication.

ABSTRACT: Antibacterial quinolones are widely used to treat bacterial infections in humans. They inhibit bacterial DNA gyrase and topoisomerase IV, whose analogous enzymes are present in mammalian mitochondria. Quinolones inhibit mitochondrial topoisomerases, thereby leading to mitochondrial DNA (mtDNA) replication suppression and cancer cell death. Meanwhile, high concentrations of quinolones are required to induce cancer cell death, possibly owing to poor delivery to the mitochondria. In this study, we synthesized nalidixic acid (NA) and ciprofloxacin (CFX) conjugated with the mitochondria-targeting moiety triphenylphosphonium (TPP), NX-TPP and CFX-TPP, to enhance mitochondrial delivery and examined their anticancer efficacy. NX-TPP and CFX-TPP markedly reduced the antibacterial activity, although

SUBMITTER: Qiao Y 

PROVIDER: S-EPMC12666482 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature