APPROACHES TO CHARACTERIZATION OF ANTIINFECTIVE AGENTS

抗感染剂的表征方法

• 批准号: 6532596
• 负责人: Mark T Hamann
• 金额: $ 10.13万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6532596
• 关键词: HIV infections; Porifera; Tunicata; X ray crystallography; algae; antifungal agents; antiinfective agents; antimalarial agents; antiprotozoal agents; antiviral agents; chemical structure function; communicable diseases; coral; cytotoxicity; drug discovery /isolation; drug screening /evaluation; enzyme inhibitors; high performance liquid chromatography; mass spectrometry; microorganism disease chemotherapy; nuclear magnetic resonance spectroscopy; opportunistic infections; saltwater environment

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.

该项目的主要重点是新的化学型用于治疗传染病的分离和表征。 这包括涉及仪器开发的研究，以快速而彻底地分析复杂的生物混合物中生物活性有机化合物。 我们的目标是将有机材料的纯化和结构确定最强大的工具集成到单个系统中，同时能够回收近95％的纯化样品进行生物学评估。 最有希望的代谢物将使用半合成，微生物转化和分子建模来研究结构活性关系（SAR）。在过去的几十年中，自然产品研究从海洋环境中产生了数千种新型有机化合物。指导这些分离的生物测定通常是抗菌，抗肿瘤，抗病毒或抗炎药。 几乎没有做任何事情来探索对艾滋病毒，艾滋病，结核病和其他传染病的活性化合物的海洋。此外，由于与常规的独立水下呼吸器（Scuba）相关的限制，因此以海洋环境为特征的大多数化合物是浅水收集的结果（-30m）。国家癌症研究所药物发现研究与开发实验室实验室的迈克尔·博伊德（Michael Boyd）表明，事实证明，群众筛查是发现完全新的化学型甚至没有怀疑具有相关生化特性的最有效方法。 该提出的研究计划的目的是收集和筛选海洋样品，以便从尚未探索的海洋深处和海洋中的艾滋病毒和艾滋病治疗。这些提取物的活性成分将使用与NMR和FTMS相连的制备和半预制的高压液相色谱（HPLC）分离。 生物活性二级代谢产物的化学结构将通过使用LC-NMR-FTM和2D NMR确定。通过合成，半合成或再隔离提供足够数量的体内测试的方法，将用于有希望的化合物。 SAR研究将利用生物活性二级代谢产物与分子建模研究的化学和微生物转化进行。

项目成果

The manzamine alkaloids.

• DOI: 10.1016/s0099-9598(03)60004-0
• 发表时间: 2003-01-01
• 期刊: The Alkaloids. Chemistry and biology
• 作者: Hu, Jin-Feng;Hamann, Mark T;Kelly, Michelle
• 通讯作者: Kelly, Michelle

Kahalalides V-Y isolated from a Hawaiian collection of the sacoglossan mollusk Elysia rufescens.

Kahalalides V-Y 从夏威夷的 Sacoglossan 软体动物 Elysia rufescens 中分离出来。

• DOI: 10.1021/np070508g
• 发表时间: 2008
• 期刊: Journal of natural products
• 影响因子: 5.1
• 作者: Rao,KarumanchiV;Na,MinKyun;Cook,JenniferC;Peng,Jiangnan;Matsumoto,Rae;Hamann,MarkT
• 通讯作者: Hamann,MarkT

Structure and absolute configuration of karlotoxin-2, an ichthyotoxin from the marine dinoflagellate Karlodinium veneficum.

• DOI: 10.1021/ja9091853
• 发表时间: 2010-03-17
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Peng, Jiangnan;Place, Allen R.;Yoshida, Wesley;Anklin, Clemens;Hamann, Mark T.
• 通讯作者: Hamann, Mark T.

Marine natural products and their potential applications as anti-infective agents.

• DOI: 10.1016/s1473-3099(03)00655-8
• 发表时间: 2003-06
• 期刊: The Lancet. Infectious diseases
• 作者: Donia M;Hamann MT
• 通讯作者: Hamann MT