Fluoroquinolone antibiotics show genotoxic effect through DNA-binding and oxidative damage.

Abstract

The fluoroquinolones (FQs) are one the most successful class of synthetic antibiotics that primarily target the type II topoisomerases. With a pursuit to evaluate their genotoxicity, the present work established moderate to good DNA-damaging properties of some of the well-known and clinically prescribed fluoroquinolone antibiotics (2nd and 3rd generation). Hypochromic shift in UV-Vis absorption titration, fluorescence quenching in competitive ethidium bromide displacement assay (with calf-thymus DNA) and in-silico studies established DNA-intercalation with binding constants of the order 104. A basic Structure Activity Relationship (SAR) has been derived from the docking results. MTT assay has been also done to evaluate the effect of these antibiotics on cell viability. The expression level of specific DNA-glycosylase enzymes responsible for repairing the oxidized DNA bases are quantified through western blot analysis. The studies revealed that fluoroquinolone antibiotics initiate the genotoxic effect at a concentration of above 50 μg/mL. Recruitment of APE1 and NEIL1 was found to be significantly increased to remove the oxidized nucleobases.