DNA Strand-Breaking Activities of Quinolone Antimicrobial Agents under Visible Light Irradiation

Abstract

The DNA strand-breaking activities of 9 quinolones, widely used as antimicrobial agents and suspected to induce photo-dermatological disorders in humans, were examined under irradiation using standard domestic fluorescent lamps. Two quinolones, tosufloxacin and enoxacin, converted the supercoiled covalently closed circular plasmid DNA to the open circular form unde* visible light irradiation. The maximum of photodynamic single strand-breaking activity for tosufloxacin was found to be 12% at 50 μm and that of enoxacin was 33% at a concentration of 2mM. The DNA strand-breaking activities of photoirradiated tosufloxacin and enoxacin were markedly inhibited by NaN3 but only partially by D-mannitol, superoxide dismutase (SOD) and catalase did not inhibit these activities. These results suggest that some quinolone antimicrobial agents can be activated by visible light and induce phototoxic DNA damage in various organisms. We should carefully investigate such phototoxic activities during the development of new quinolones to avoid producing phototoxic disorders in man. © 1994, The Pharmaceutical Society of Japan. All rights reserved.