Anti-Malarial Drug Leads from Fungi

来自真菌的抗疟疾药物

• 批准号: 10288060
• 负责人: NICHOLAS H. OBERLIES
• 金额: $ 22.59万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-21 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10288060
• 关键词: Address; Aflatoxins; Antimalarials; Artemisinins; Biological; Biological Assay; Biology; Blood; Chemicals; Chemistry; Combined Modality Therapy; Cytochalasins; DNA; Data; Development; Disease; Drug resistance; Evaluation; Fermentation; Growth; In Situ; Laboratories; Lead; Libraries; Life Cycle Stages; Liver; Malaria; Mammalian Cell; Manuscripts; Measurement; Medicine; Methods; Mission; Molecular; Morphology; Mycotoxins; Natural Products; Natural Products Chemistry; Nobel Prize; Parasites; Parasitic Diseases; Parasitology; Penicillins; Pharmaceutical Preparations; Phenotype; Physiology; Plasmodium falciparum; Productivity; Protocols documentation; Quinine; Recording of previous events; Reproducibility; Research Methodology; Resistance; Sampling; Source; Structure; Taxonomy; Techniques; Testing; The science of Mycology; Time; Toxic effect; Trichothecenes; asexual; base; cancer cell; cell growth; chemotherapy; cytotoxic; cytotoxicity; drug discovery; fungus; indexing; novel therapeutics; prevent; quinoline; scale up; screening; tool development; transmission process

Project Summary There is a need for new antimalarial drug leads, particularly for treating drug resistant malaria. Fungi have been the source of many drug leads, with penicillin and the statins as two of the most prominent examples. We hypothesize that fungi harbor antimalarial drug leads, and we are addressing this via a team with expertise in mycology (Mycosynthetix/Pearce), natural products chemistry (UNCG/Oberlies), and parasitology/malaria (UGA/Kyle). In the examination of 40,000 fungal cultures from the Mycosythetix library, we have implemented biological and chemical protocols to prioritize our efforts. In doing so, we have now selected 8 fungal cultures that have potent antimalarial activity, minimal cytotoxicity to mammalian cells, and do not biosynthesize common nuisance compounds (i.e. mycotoxins). That averages to the analysis of ~1 fungal culture per quarter over this 2 year project. Our team is poised to isolate, elucidate, and evaluate antimalarial drug leads from these cultures. In addition, we will prioritize the 1 to 2 best leads, such that ample materials are produced for more in depth biological evaluation.

项目摘要 需要新的抗疟疾药物，特别是用于治疗抗药性疟疾的药物。真菌一直是 许多药物的来源，青霉素和他汀类药物是最突出的两个例子。我们 假设真菌含有抗疟疾药物，我们正在通过一个具有以下专业知识的团队来解决这个问题 真菌学(真菌学/皮尔斯)、天然产物化学(UNG/Oberlie)和寄生虫学/疟疾 (UGA/Kyle)。 在对Mycoythetix文库的40,000种真菌培养物的检查中，我们实施了生物学和 化学协议来确定我们的工作的优先顺序。在这样做的过程中，我们现在选择了8种真菌培养物 抗疟疾活性，对哺乳动物细胞的细胞毒性最小，不会生物合成常见的有害物质 化合物(即霉菌毒素)。这意味着在这两年中，平均每季度有1种真菌培养 项目。我们的团队准备从这些培养物中分离、阐明和评估抗疟疾药物的先导。在……里面 此外，我们将优先选择1到2个最佳线索，以便为更深入的研究提供充足的材料 生物评价。