抗克氏锥虫的5-硝基-2-呋喃基衍生物：初步体内研究

5-Nitro-2-furyl derivative actives against Trypanosoma cruzi: preliminary in vivo studies.

作者信息

Cabrera Eliana, Murguiondo Mariana González, Arias Marelina González, Arredondo Carolina, Pintos Cristina, Aguirre Gabriela, Fernández Marcelo, Basmadjián Yester, Rosa Raquel, Pacheco José Pedro, Raymondo Stella, Di Maio Rossanna, González Mercedes, Cerecetto Hugo

机构信息

Departamento de Química Orgánica, Facultad de Química/Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.

出版信息

Eur J Med Chem. 2009 Oct;44(10):3909-14. doi: 10.1016/j.ejmech.2009.04.015. Epub 2009 Apr 14.

DOI:10.1016/j.ejmech.2009.04.015

PMID:19446929

Abstract

Ten 5-nitro-2-furyl derivatives, with good to excellent in vitro anti-Trypanosoma cruzi activity, and nifurtimox were tested oral and intraperitoneally on healthy animals for its acute toxicity on murine models. According to animals' survival percentage, organ histological results, biochemical and haematological findings, three new derivatives, with toxicity like nifurtimox, were selected to test in vivo as antichagasic agents. Clearly, dependences between chemical structure and both acute toxicity and in vivo anti-T. cruzi activity were observed. 4-Hexyl-1-[3-(5-nitro-2-furyl)-2-propenylidene]semicarbazide displayed good profile as anti-T. cruzi agent and better acute toxicity profile than nifurtimox.

摘要

对10种具有良好至优异体外抗克氏锥虫活性的5-硝基-2-呋喃基衍生物以及硝呋替莫进行了口服和腹腔注射，以检测其对健康动物的急性毒性，实验采用小鼠模型。根据动物存活率、器官组织学结果、生化和血液学检查结果，选择了三种毒性与硝呋替莫相似的新衍生物作为抗恰加斯病药物进行体内试验。显然，观察到了化学结构与急性毒性及体内抗克氏锥虫活性之间的相关性。4-己基-1-[3-(5-硝基-2-呋喃基)-2-亚丙烯基]氨基脲作为抗克氏锥虫药物表现出良好的特性，且急性毒性比硝呋替莫更好。