MODE OF ACTION OF TRYPANOCIDAL CATIONIC DRUGS

这项建议的目的是详细研究 龙胆紫和其他物质的作用机理 阳离子药物发挥其杀锥虫作用，代谢 克氏锥虫和哺乳动物对这些化合物的研究 系统。这些研究的目标将是阐明 宿主和寄生虫之间的差异可被利用 用于化学预防的目的。阳离子药物对血管内皮细胞生长的影响 细胞膜将是一个集中的领域，因为 龙胆紫对线粒体氧化的解偶联作用 最近发现了磷酸化。的第二部分 该建议将包括探索化学预防 龙胆紫光动力作用的研究近况 演示了。最后，研究的第三部分将 关注龙胆紫在锥虫体内的代谢 克鲁兹和哺乳动物系统。这些研究将澄清这一角色 对寄生虫抗性的代谢转化的研究 龙胆紫的化学预防作用及重要性 代谢物的毒性和致癌潜力。

The objectives of this proposal are to study, in detail, the mechanism or mechanisms by which gentian violet and other cationic drugs exert their trypanocidal action, and the metabolism of these compounds by Trypanosona cruzi and mammalian systems. The goal of these studies will be the elucidation of differences between host and parasite that could be exploited for chemoprophylactic purposes. The effect of cationic drugs on cellular membranes will be one area of concentration since an uncoupling effect of gentian violet on mitochondrial oxicative phosphorylation has recently been found. The second portion of the proposal will consist in exploring the chemoprophylactic potential of the photodynamic action of gentian violet recently demonstrated. Finally, the third portion of the studies will concentrate on the metabolism of gentian violet in Trypanosoma cruzi and mammalian systems. There studies will clarify the role of metabolic transformations in parasite resistance to chemoprophylaxis and the importance of gentian violet metabolites in its toxicity and carcinogenic potential.