APPROACHES TO CHARACTERIZATION OF ANTIINFECTIVE AGENTS

本项目的主要焦点是分离和表征 用于治疗传染病的新的化学类型。这 包括涉及开发用于 快速透彻地分析络合物中的生物活性有机化合物 生物混合物。我们的目标是集成最强大的工具 可用于有机化合物的提纯和结构测定 将材料整合到单个系统中，同时能够回收近95 用于生物学评价的纯化样品的百分比。最多的 有希望的代谢物的结构活性将被研究 关系(SAR)使用半合成、微生物转化和 分子建模。 在过去的几十年里，对天然产品的研究已经取得了成果 海洋环境中数以千计的新型有机化合物。这个 指导这些分离的生物检测通常是抗菌的， 抗肿瘤、抗病毒或抗炎。几乎没有采取什么措施来 探索海洋，寻找具有抗艾滋病毒、艾滋病、结核病活性的化合物 以及其他传染病。此外，由于限制， 与传统的自给式水下呼吸有关 仪器(Scuba)，大多数化合物的表征来自 海洋环境是浅水采集(-30米)的结果。 药物发现研究和实验室的迈克尔·博伊德博士 国家癌症研究所的研究表明， 事实证明，筛查是发现 全新的化学类型甚至没有被怀疑有相关的生化 属性。这项拟议的研究计划的目标是 收集和筛选可能治疗艾滋病毒和艾滋病的海洋样本 来自海洋深处和位置的艾滋病OI 未被开发的。 这些提取物的活性成分(S)显示出良好的活性 将使用制备性和半制备性高压分离 与核磁共振和傅立叶变换红外光谱联用的高效液相色谱。化学物质 生物活性次生代谢物的结构将是 用LC-核磁共振-傅立叶变换红外光谱和二维核磁共振进行了测定。提供以下服务的方法 通过合成、半合成进行体内测试的足够数量 否则将解决有希望的化合物的重新分离问题。合成孔径雷达研究 将利用化学和微生物转化 生物活性次生代谢物与分子结合 模特儿研究。

The primary focus of this project is the isolation and characterization of new chemotypes for the treatment of infectious diseases. This includes research involving the development of instrumentation for the rapid and thorough analysis of bioactive organic compounds in complex biological mixtures. Our goal is to integrate the most powerful tools available for the purification and structure determination of organic materials into a single system while being able to recover nearly 95 percent of the purified sample for biological evaluation. The most promising metabolites will be studied for structure-activity relationships (SAR) using semi-synthesis, microbial transformations and molecular modeling. Natural product research during the last few decades has yielded thousands of novel organic compounds from the marine environment. The bioassays guiding these isolations typically have been antimicrobial, antitumor, antiviral or antiinflammatory. Little has been done to explore the oceans for compounds with activity against HIV, AIDS OI, TB and other infectious diseases. Additionally, because of the limits associated with the conventional self-contained underwater breathing apparatus (SCUBA), the majority of the compounds characterized from the marine environment are the results of shallow water collections (-30m). Dr. Michael Boyd, of the Laboratory of Drug Discovery Research and Development at the National Cancer Institute indicates that mass screening has proved to be the most effective means of discovering entirely new chemotypes not even suspected to have relevant biochemical properties. The objective of this proposed research program is to collect and screen marine samples for possible treatments of HIV and AIDS OI from depths and locations in the ocean which have remained unexplored. The active component(s) of those extracts showing promising activity will be isolated using preparative and semi-preparative high pressure liquid chromatography (HPLC) interfaced with NMR and FTMS. The chemical structures of the biologically active secondary metabolites will be determined with the use of LC-NMR-FTMS and 2D NMR. Methods for providing sufficient quantities for in vivo testing via synthesis, semi-synthesis or reisolation will be addressed for promising compounds. SAR studies will be conducted utilizing chemical and microbial transformations of biologically active secondary metabolites combined with molecular modeling studies.