LIPIDS OF LEISHMANIAS AND TRYPANOSOMES

本项目的长期目标是确定和研究 控制利什曼原虫的新的化学治疗方法 具有重要医学意义的美洲锥虫感染， 通过利用脂质生物化学的知识， 负责的锥虫鞭毛虫的特征是 真菌和其他植物，而不是脊椎动物。 立即 实现这一目标的具体目标是调查： a）植物的甾醇、磷脂和鞘糖脂生物化学 代表性利什曼原虫种的生命周期阶段， 克氏锥虫菌株，B）生物化学扰动， 和生长障碍，由针对特定 酶促反应，和c）最多的作用机制 这些药物的有效性。 生命周期各阶段都要培养 在暴露于药物和放射性的组织细胞内和组织细胞外， 稳定同位素示踪剂，以及对生长和 通过群体计数和脂质代谢评估的脂质代谢 采用色谱法（CC、TLC、HPLC、GLC）进行分析，以及 光谱法（GC/MS、1H和13 C NMR、UV/维斯、液体闪烁） 方法论。 通过这些方法，对酶反应有活性的药物 利什曼原虫和锥虫所特有的，或者具有 与人类的类似反应不同， 确定，以及它们对寄生虫的选择性毒性， 为宿主组织细胞建立。

The long term objective of this project is to identify and to study novel chemotherapeutic approaches to the control of leishmanial and American trypanosomal infections of substantial medical importance, by exploiting knowledge that aspects of the lipid biochemistry of the responsible trypanosomatid flagellates are characteristic of fungi and other plants and not of vertebrates. The immediate specific aims to realize this objective are to investigate the: a) sterol, phospholipid and glycosphingolipid biochemistry of the life-cycle stages of representative leishmania species and Trypanosoma cruzi strains, b) perturbations of that biochemistry, and impairment of growth, cause by drugs targeted to specific enzymatic reactions, and c) mechanisms of action of the most effective of those drugs. Life-cycle stages are to be cultured within and without tissue cells exposed to drugs and radio- and stable isotopic tracers, and the consequences to growth and to lipid metabolism assessed by population enumeration, and by lipid analyses employing chromatographic (CC, TLC, HPLC, GLC), and spectrometric (GC/MS, 1H & 13C NMR, UV/VIS, liquid scintillation) methodologies. By these means, drugs active on enzymatic reactions unique to leishmanias and trypanosomes, or with properties different from those of analogous reactions in man, are to be identified, and their selective toxicities for the parasites and for host tissue cells established.