Anti-Malarial Drug Leads from Fungi

来自真菌的抗疟疾药物

基本信息

批准号：
10408834
负责人：
NICHOLAS H. OBERLIES
金额：
$ 17.29万
依托单位：
UNIVERSITY OF NORTH CAROLINA GREENSBORO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-21 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10408834
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

项目摘要

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药铅，特别是治疗耐药性疟疾。真菌一直是许多药物铅的来源，青霉素和他汀类药物是两个最突出的例子。我们假设真菌港口抗疟药铅，我们正在通过一支具有专业知识的团队来解决这一问题真菌学（Mycosynthetix/Pearce），天然产品化学（UNCG/Oberlies）和寄生虫学/疟疾（uga/kyle）。在检查Mycosythetix图书馆的40,000种真菌培养物中，我们实施了生物学和化学方案以优先考虑我们的努力。在这样做的过程中，我们现在选择了8种有效的真菌文化抗疟疾活性，对哺乳动物细胞的细胞毒性最小，并且不会生物合成常见的滋扰化合物（即霉菌毒素）。在这两年中，平均每季度分析〜1个真菌培养项目。我们的团队准备隔离，阐明和评估这些培养物的抗疟药铅。在此外，我们将优先考虑1到2个最佳线索，以便产生足够的材料以进行更多的深度生物评估。