In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives
In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives
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DOI：
10.1128/aac.41.12.2729
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发表时间：
1997-12-01
影响因子：
4.9
通讯作者：
Edlind, TD
中科院分区：
文献类型：
--
作者：
Katiyar, SK;Edlind, TD
最近的报道描述了我们成功地治疗了艾滋病患者的脑炎原虫感染。为了比较阿苯达唑、阿苯达唑亚砜和其它苯并咪唑类化合物的活性，我们建立了一个体外系统，该系统涉及用大肠杆菌感染绿色猴肾细胞（E6）单层。孢子发育。14天后，测定苯并咪唑类对孢子产生的影响。测试的14种衍生物中的10种，包括阿苯达唑，在1至10 ng/ml的浓度下具有抑制作用。在1或2位修饰的衍生物活性较低。阿苯达唑亚砜的抑制作用是阿苯达唑的1.7倍，但对E6细胞的毒性显著降低，这一发现解释了该化合物的临床疗效。潜在的替代阿苯达唑进行了讨论。无阿苯达唑耐药大肠杆菌。在体外选择后获得突变体。
Recent reports have described We successful treatment of Encephalitozoon intestinalis infection in AIDS patients with albendazole. However, this compound is rapidly metabolized in vivo to albendazole sulfoxide, and furthermore it is only 1 of about 15 commercially developed benzimidazole derivatives, To compare the activities of albendazole, albendazole sulfoxide, and other benzimidazoles, an in vitro system involving infection of green monkey kidney cell (E6) monolayers with E. intestinalis spores was developed. After 14 days, the effects of benzimidazoles on spore production were determined, Ten of fourteen derivatives tested, including albendazole, were inhibitory at concentrations of 1 to 10 ng/ml. Derivatives modified at the 1 or 2 position were less active. Albendazole sulfoxide was 1.7-fold more inhibitory than albendazole but significantly less toxic to E6 cells, a finding that explains-the clinical efficacy of this compound. Potential alternatives to albendazole are discussed. No albendazole-resistant E. intestinalis mutants were obtained following in vitro selection.