Anti-Toxoplasma gondii activities and structure-activity relationships of novel fluoroquinolones related to trovafloxacin.
Anti-Toxoplasma gondii activities and structure-activity relationships of novel fluoroquinolones related to trovafloxacin.
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与曲伐沙星相关的新型氟喹诺酮类药物的抗弓形虫活性和构效关系。
DOI：
10.1128/aac.43.7.1783
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发表时间：
1999
影响因子：
4.9
通讯作者：
Remington,JS
中科院分区：
文献类型：
--
作者：
Khan,AA;Araujo,FG;Brighty,KE;Gootz,TD;Remington,JS
评价了11个与曲伐他汀密切相关的新型氟喹诺酮类化合物的体外抗弓形虫活性，并分析了它们的构效关系。曲伐他汀对T. 11个类似物的IC_（50）在0.53 ~ 14.09 μM之间。6个类似物的IC 50低于曲伐他汀。对化合物的构效关系的研究表明，在1，8-萘二酮环的C-5位、氮杂双环己烷环的C-2位或氮杂双环己烷环的6位-NH 2上添加-CH 3可使活性增加4 - 6倍。此外，在1，8-萘烷酮环的N-1处用环丙基取代2，4-二氟苯基使活性增加两倍，并且使-NH 2一原子进一步远离氮杂双环己烷环降低活性。萘啶酮和喹诺酮类似物之间没有差异。这些结果表明，与抗T活性药物相关的化合物的结构-活性研究。gondii可用于生产对寄生虫具有更有效活性的化合物。
Eleven novel fluoroquinolones closely related to trovafloxacin were evaluated for their in vitro activity againstToxoplasma gondii, and their structure-activity relationships were examined. The 50% inhibitory concentration (IC50) of trovafloxacin againstT. gondiiwas 2.93 μM; the IC50of the 11 analogs ranged from 0.53 to 14.09 μM. Six analogs had IC50s lower than that of trovafloxacin. Examination of the structure-activity relationships of the compounds revealed that addition of a -CH3at C-5 of the 1,8-naphthyridone ring, at C-2 of the azabicyclohexane ring, or on the -NH2at the 6 position 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 the -NH2one atom further away from the azabicyclohexane ring decreased activity. There was no difference between the naphthyridone and quinolone analogs. These results indicate that structure-activity studies of compounds related to drugs active againstT. gondiimay be useful in producing compounds with more potent activities against the parasite.