Anti-Toxoplasma gondii activities and structure-activity relationships of novel fluoroquinolones related to trovafloxacin

Eleven novel fluoroquinolones closely related to trovafloxacin were evaluat ed for their in vitro activity against Toxoplasma gondii, and their structu re-activity relationships were examined, The 50% inhibitory concentration ( IC50) of trovafloxacin against T. gondii was 2.93 mu M; the IC50 of the 11 analogs ranged from 0.53 to 14.09 mu M Six analogs had IC(50)s lower than t hat of trovafloxacin. Examination of the structure-activity relationships o f the compounds revealed that addition of a -CH3 at C-5 of the 1,8-naphthyr idone ring, at C-2 of the azabicyclohexane ring, or on the -NH2 at the 6 po sition of the azabicyclohexane ring resulted in a four- to sixfold increase in activity. Moreover, replacement of 2,4-difluorophenyl by cyclopropyl at N-1 of the 1,8-naphthyridone ring increased activity twofold, and moving t he -NH2 one atom further away from the azabicyclohexane ring decreased acti vity. There was no difference between the naphthyridone and quinolone analo gs. These results indicate that structure-activity studies of compounds rel ated to drugs active against T. gondii may be useful in producing compounds with more potent activities against the parasite.