INHIBITORY ACTIVITIES OF GATIFLOXACIN (AM-1155), A NEWLY DEVELOPED FLUOROQUINOLONE, AGAINST BACTERIAL AND MAMMALIAN TYPE-II TOPOISOMERASES

We determined the inhibitory activities of gatifloxacin against Staphy lococcus aureus topoisomerase IV, Escherichia coli DNA gyrase, and HeL a cell topoisomerase II and compared them with those of several quinol ones. The inhibitory activities of quinolones against these type II to poisomerases significantly correlated with their antibacterial activit ies or cytotoxicities (correlation coefficient [I] = 0.926 for S. aure us, r = 0.972 for E. coli, and r = 0.648 for HeLa cells), Gatifloxacin possessed potent inhibitory activities against bacterial type II topo isomerases (50% inhibitory concentration [IC50] = 13.8 mu g/ml for S. aureus topoisomerase IV; IC50 = 0.109 mu g/mi for E, coli DNA gyrase) but the lowest activity against HeLa cell topoisomerase II (IC50 = 265 mu g/ml) among the quinolones tested, There was also a significant co rrelation between the inhibitory activities of quinolones against S, a ureus topoisomerase IV and those against E. coli DNA gyrase (r = 0.969 ). However, the inhibitory activity against HeLa cell topoisomerase II did not correlate with that against either bacterial enzyme, The IC50 of gatifloxacin For HeLa cell topoisomerase II was 19 and was more th an 2,400 limes higher than that for S. aureus topoisomerase TV and tha t for E. coli DNA gyrase. These ratios were higher than those for othe r quinolones, indicating that gatifloxacin possesses a higher selectiv ity for bacterial type II topoisomerases.