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克氏锥虫(前鞭毛体)新型生长抑制剂的设计、合成及生物学评价

Design, synthesis, and biological evaluation of new growth inhibitors of Trypanosoma cruzi (epimastigotes).

作者信息

Schvartzapel A J, Zhong L, Docampo R, Rodriguez J B, Gros E G

机构信息

Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.

出版信息

J Med Chem. 1997 Jul 18;40(15):2314-22. doi: 10.1021/jm9607616.

Abstract

As a continuation of our project aimed at the search for new chemotherapeutic agents against Chagas' disease, several drugs structurally related to the insect growth regulator Fenoxycarb and the naturally occurring juvenile hormone of insects were designed, synthesized, and evaluated as antiproliferative agents against the parasite responsible of this disease. Isoprenoid derivatives (compounds 33, 34, 36, and 37) were potent growth inhibitors of Trypanosoma cruzi epimastigotes. In addition, taking into account the high activity observed for compound 30 and the inhibitory action of related compounds, the allyl ether moiety bonded at the polar extreme of these inhibitors proved to be a promising group for the design of new drugs.

摘要

作为我们旨在寻找治疗恰加斯病新化疗药物的项目的延续,我们设计、合成并评估了几种与昆虫生长调节剂苯氧威以及昆虫天然存在的保幼激素结构相关的药物,作为针对引发该疾病的寄生虫的抗增殖剂。类异戊二烯衍生物(化合物33、34、36和37)是克氏锥虫前鞭毛体的强效生长抑制剂。此外,考虑到化合物30所观察到的高活性以及相关化合物的抑制作用,这些抑制剂极性末端连接的烯丙基醚部分被证明是设计新药的一个有前景的基团。

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