Aguirre Gabriela, Boiani Lucía, Cerecetto Hugo, Di Maio Rossanna, González Mercedes, Porcal Williams, Denicola Ana, Möller Matías, Thomson Leonor, Tórtora Verónica
Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Bioorg Med Chem. 2005 Dec 1;13(23):6324-35. doi: 10.1016/j.bmc.2005.05.020. Epub 2005 Aug 22.
The results of a study on the use of Hansch's series design, cluster methodology, for the generation of new benzo[1,2-c]1,2,5-oxadiazole N-oxide derivatives as antitrypanosomal compounds are described. In vitro activity of these compounds was tested against Tulahuen 2 strain of Trypanosoma cruzi. Clearly, the Hansch methodology allowed identifying two cluster-substituents suitable for further structural modifications. The most effective drugs, derivatives 11, 18, and 21, with 50% inhibitory concentration (IC(50)) of the same order as that of the reference drug, represent an excellent structural point of chemical modifications for the design of future drugs. Preliminary results from the study of the mechanism of action of these benzofuroxans point to perturbation of the mitochondrial electron chain, inhibiting parasite respiration.
本文描述了一项关于使用汉斯ch系列设计、聚类方法来生成新型苯并[1,2-c]1,2,5-恶二唑N-氧化物衍生物作为抗锥虫化合物的研究结果。测试了这些化合物对克氏锥虫图拉洪2株的体外活性。显然，汉斯ch方法能够识别出两个适合进一步结构修饰的聚类取代基。最有效的药物，即衍生物11、18和21，其50%抑制浓度（IC(50)）与参考药物相当，是未来药物设计中化学修饰的极佳结构点。对这些苯并呋咱作用机制的初步研究结果表明，其干扰线粒体电子链，抑制寄生虫呼吸。
