NOVEL NEMATODE SPECIFIC ANTHELMINTICS AND NEMATICIDES

我们的目的是开发新的杀线虫剂和驱虫剂 其是线虫特异性的并且具有新颖的模式， 行动上 我们的方法包括对线虫的详细研究 谷氨酸和5-羟色胺受体 （血清素）。 第一阶段包括行为和电生理 鉴定对线虫GLU有活性的化合物的实验 和血清素受体的基因实验 快速筛选对这些受体有活性的其它化合物， 以及配体结合分析的发展。 在第二阶段，我们将使用筛选来识别新的电极导线 对线虫GLU和血清素有活性的化合物 受体。 我们将使用配体结合试验来进行 这些先导化合物类似物的构效关系研究 为了发现可以增加其活性的化学修饰， 对线虫受体的特异性， 同源哺乳动物受体。 修改最 线虫特异性化合物从这项工作中出现，指导 通过对寄生虫的体内测定（III期），将产生新的， 线虫特异性驱虫剂和杀线虫剂。

Our purpose is to develop new nematicides and anthelmintics which are nematode-specific and which have a novel mode of action. Our approach involves detailed studies of the nematode receptors for glutamic acid (GLU) and 5-hydroxytryptamine (serotonin). Phase I includes behavioral and electrophysiological experiments to identify compounds active at the nematode GLU and serotonin receptors, genetic experiments designed to produce rapid screens for additional compounds active at these receptors, and the development of ligand-binding assays. During phase II we will use the screens to identify novel lead compounds which are active at the nematode GLU and serotonin receptors. We will use the ligand-binding assay to perform structure-activity studies on analogues of these lead compounds in order to discover chemical modifications which increase their specificity for the nematode receptor as compared to the homologous mammalian receptors. Modification of the most nematode-specific compounds to emerge from this work, guided by in vivo assays on parasites (phase III), will yield novel, nematode-specific anthelmintics and nematicides.