Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro
Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro
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DOI：
10.1128/aac.41.7.1541
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发表时间：
1997-07-01
影响因子：
4.9
通讯作者：
Didier, ES
中科院分区：
文献类型：
--
作者：
Didier, ES
目前，治疗艾滋病患者微孢子虫病最常用的两种药物是阿苯达唑和福马西林。阿苯达唑治疗脑孢子虫播散性感染有效。但对贝氏肠细胞体感染有不同程度的有效。福马西林外用治疗肺炎脑炎或肠脑炎有效，但毒性太大，不适合全身使用，本研究测定了福马西林类似物TNP-470的体外抗微孢子虫活性。对肠道和角质形成的MIC50分别为0.35+/-0.21和0.38+/-0.11 ng/ml，与烟美西林的MIC50 S相当，分别为0.515+/-0.002和0.81+/-0.014 ng/ml；阿苯达唑对肠杆菌的MIC508.0+/-4.23 ng/ml，与S相似(P<；TNP-470对RK-13细胞的MIC50为55.0+/-7.07 ng/ml。如果TNP-470在感染的同时给药或在7天后开始治疗，则TNP-470可抑制肠杆菌在RK-13细胞中的复制。此外，用10 ng/ml的TNP-470处理受感染的培养物2周，然后停止用药，在接下来的3周内没有显著增加肠杆菌的脱落，因为TNP-470对肠杆菌和角质弧菌都有作用，而且TNP-470在体内被发现毒性较小，TNP-470可能是一种有前途的治疗微孢子虫病的新药。
Presently, the two most commonly used drugs for treating microsporidiosis in persons with AIDS are albendazole and fumagillin. Albendazole is effective for treating disseminated infections due to Encephalitozoon spp. but is variably effective against Enterocytozoon bieneusi infections. Fumagillin is highly effective when used topically to treat ocular infections with Encephalitozoon hellem or Encephalitozoon intestinalis but is too toxic for systemic use, In this study, the fumagillin analog TNP-470 was assayed for antimicrosporidial activity in vitro. The MICs of TNP-470 at which 50% of isolates were killed (MIC(50)s) were 0.35 +/- 0.21 and 0.38 +/- 0.11, ng/ml for a intestinalis and Vittaforma corneae, respectively, and were similar to the MIC(50)s of fumagillin for these organisms, which were 0.515 +/- 0.002 and 0.81 +/- 0.014 ng/ml, respectively, The MIC50 of albendazole for B. intestinalis was 8.0 +/- 4.23 ng/ml, significantly less (P < 0.01) than its MIC50 for V. corneae, which was 55.0 +/- 7.07 ng/ml. TNP-470 inhibited replication of E. intestinalis in RK-13 cells if it was given at the same time as infection or if treatment was initiated 7 days later. In addition, treatment of the infected cultures with TNP-470 at a dose of 10 ng/ml for 2 weeks, followed by discontinuation of the drug treatment, resulted in no significant increase in E. intestinalis shedding during the following 3 weeks in culture, Because TNP-470 acts against both E. intestinalis and V. corneae, and because TNP-470 was found by others to be less toxic in vivo, TNP-470 may be a promising new drug for the treatment of microsporidiosis.