吖啶化合物对利什曼原虫前鞭毛体的体外细胞毒性
Cytotoxicity of acridine compounds for Leishmania promastigotes in vitro.
作者信息
Werbovetz K A, Lehnert E K, Macdonald T L, Pearson R D
机构信息
Department of Chemistry, University of Virginia, Charlottesville 22901.
出版信息
Antimicrob Agents Chemother. 1992 Feb;36(2):495-7. doi: 10.1128/AAC.36.2.495.
Abstract
The effect of mammalian and bacterial topoisomerase II inhibitors on Leishmania promastigotes was studied in vitro. Parasites were incubated with drugs, and cytotoxicity was assessed on the basis of the loss of flagellar motility and cell lysis after 48 h. 9-Aminoacridines, which are structurally related to the known antileishmanial compounds quinacrine and chlorpromazine, showed activity against the parasite at concentrations in the range of 10 to 20 microM. Adriamycin showed far less activity, while etoposide and several quinolones were inactive at 100-microM concentrations. These results demonstrate that a particular structural class of compounds is cytotoxic to Leishmania species. The unique structure-activity relationship discovered suggests that leishmanial topoisomerase II could be a useful target for chemotherapy.
摘要
在体外研究了哺乳动物和细菌拓扑异构酶II抑制剂对利什曼原虫前鞭毛体的作用。将寄生虫与药物一起孵育，并在48小时后根据鞭毛运动能力的丧失和细胞裂解情况评估细胞毒性。9-氨基吖啶在结构上与已知的抗利什曼化合物奎纳克林和氯丙嗪相关，在10至20微摩尔浓度范围内对寄生虫显示出活性。阿霉素的活性要低得多，而依托泊苷和几种喹诺酮在100微摩尔浓度下无活性。这些结果表明，特定结构类别的化合物对利什曼原虫具有细胞毒性。所发现的独特构效关系表明，利什曼原虫拓扑异构酶II可能是化疗的一个有用靶点。
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