TNP-470 is an effective antimicrosporidial agent
TNP-470 is an effective antimicrosporidial agent
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DOI：
10.1086/517390
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发表时间：
1998-02-01
影响因子：
6.4
通讯作者：
Weiss, LM
中科院分区：
文献类型：
--
作者：
Coyle, C;Kent, M;Weiss, LM
微孢子虫在AIDS患者中引起腹泻和消耗综合征，对微孢子虫的治疗取得了有限的成功。烟曲霉素（Fumagillin）是一种天然分泌的水不溶性抗生素，具有抗微孢子虫的体外活性，并已成功地用于治疗AIDS患者的浅表性角膜炎，但全身治疗受到目前可用的烟曲霉素盐的毒性的限制。TNP-470是烟曲霉素的半合成类似物，在体外和无胸腺裸鼠微孢子虫病模型中进行了研究。用脑孢子虫科的微孢子虫感染RK 13细胞，并在第3天用TNP-470处理。该试剂非常有效，ID 50（与对照相比的50%抑制剂量）为0.001 μ g/mL。TNP-470还表现出对兔脑炎原虫的体内活性，在感染的无胸腺小鼠中具有延长的存活和预防腹水的发展。这些数据表明烟曲霉素衍生物TNP-470是用于治疗微孢子虫病的有希望的药剂。
Therapy for microsporidia, which cause diarrhea and a wasting syndrome in persons with AIDS, has had limited success, Fumagillin, a naturally secreted water-insoluble antibiotic, has in vitro activity against microsporidia and has been used successfully in the treatment of superficial keratitis in patients with AIDS, but systemic therapy has been limited by toxicity of the currently available fumagillin salt. TNP-470, a semisynthetic analogue of fumagillin, was studied in vitro and in the athymic nude mouse model of microsporidiosis. RK13 cells were infected with microsporidia of the family Encephalitozoonidae and treated at day 3 with TNP-470. This agent was highly effective, with an ID50 (50% inhibitory dose compared with control) of 0.001 mu g/mL. TNP-470 also demonstrated in vivo activity against Encephalitozoon cuniculi, with prolonged survival and the prevention of the development of ascites in infected athymic mice, These data suggest that the fumagillin derivative TNP-470 is a promising agent for the treatment of microsporidiosis.