Tropical Disease Drug Discovery from Marine Cyanobacteria in Panama

从巴拿马海洋蓝藻中发现热带疾病药物

• 批准号: 7557522
• 负责人: Marcy J Balunas
• 金额: $ 7.96万
• 依托单位: SMITHSONIAN INSTITUTION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-15 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7557522
• 关键词: Adverse effects; Area; Biodiversity; Biological Assay; Biological Factors; Chagas Disease; Characteristics; Clinical; Collection; Communicable Diseases; Cyanobacterium; Data; Dengue; Deposition; Development; Evaluation; Exhibits; Fractionation; Future; Habitats; Health; Infection; International; Leishmaniasis; Life; Liquid Chromatography; Malaria; Malignant Neoplasms; Marines; Mentored Research Scientist Development Award; Mentors; Mentorship; Methods; Oceans; Organic solvent product; Panama; Pharmacologic Substance; Research; Resistance; Resistance development; Screening procedure; Source; Specimen; Structure; Techniques; Training; Tropical Disease; Vacuum; Work; base; combinatorial chemistry; coral; cytotoxicity; cytotoxicity test; drug discovery; effective therapy; improved; in vitro activity; pre-clinical; voucher

DESCRIPTION (provided by applicant): Tropical parasitic and infectious diseases (e.g., malaria, Chagas' disease, leishmaniasis, and Dengue fever) pose enormous global health threats, but are largely ignored by the major pharmaceutical companies. Treatments for tropical diseases are generally prohibitively expensive for many people living in areas of high rates of infection. Furthermore, many tropical diseases are developing resistance to currently available treatments, or are without effective treatments. Natural products contain highly diverse structures with unique characteristics not readily accessible through synthetic or combinatorial chemistry. The hypothesis for this research is that marine species from the biologically diverse oceans in Panama will yield chemically diverse compounds, some of which will inhibit the infection and/or spread of tropical diseases. These new active compounds from marine cyanobacteria may also provide increased efficacy, ability to overcome resistance, and/or reduced side effects as compared with existing agents, and thus could be appropriate for future preclinical and clinical development. The International Cooperative Biodiversity Group (ICBG) based in Panama entitled "Ecologically Directed Drug Discovery in Panama" has been involved in a nine year effort, working to identify treatments for malaria, Chagas' disease, leishmaniasis, and cancer. New collections of marine specimens are needed to continue the search for improved, less expensive treatments for tropical diseases. Thus, the following specific aims (SA) are proposed: SA 1, use ecologically guided marine collection techniques to collect specimens for screening; SA 2, extract marine specimens, perform pre-fractionation of extracts, and send for screening for in vitro activity against tropical diseases including malaria, Chagas' disease, and leishmaniasis, as well as for cytotoxicity testing - prioritize fractions for further analysis based on bioassay results: fractions that exhibit potent activity in one assay with minimal effect on other assays and with corresponding low cytotoxicity will continue on for further fractionation and compound isolation; SA 3, conduct bioassay-guided fractionation to isolate and identify compounds that act against these tropical diseases. These specific aims provide the focus for this International Research Scientist Development Award (IRSDA), involving U.S. and foreign mentors who have collaborated for years on the Panama ICBG, and who have in place a tremendous plan for the training and mentorship of the candidate.

描述（由申请人提供）：热带寄生虫和传染病（例如疟疾，查加斯疾病，利什曼病和登革热）构成了巨大的全球健康威胁，但在很大程度上被主要制药公司忽略了。对于许多生活在高感染率地区的人来说，热带疾病的治疗通常非常昂贵。此外，许多热带疾病正在对当前可用的治疗产生抗药性，或者没有有效的治疗方法。天然产品包含具有独特特征的高度多样性结构，无法通过合成或组合化学易于访问。这项研究的假设是，来自巴拿马生物多样化海洋的海洋物种将产生化学多样的化合物，其中一些化合物会抑制热带疾病的感染和/或传播。与现有药物相比，这些新的活性化合物也可能提供提高的疗效，克服抗性能力和/或副作用，因此可能适合将来的临床前和临床发育。总部位于巴拿马的国际合作生物多样性小组（ICBG）题为“巴拿马生态定向的药物发现”已经参与了九年的努力，旨在识别有关疟疾，查加斯病，利什曼病和癌症的治疗方法。需要新的海洋标本收集，以继续寻找改进的热带疾病治疗方法。因此，提出了以下特定目的（SA）：SA 1，使用生态引导的海洋收集技术来收集标本进行筛查； SA 2，提取物海洋样本，进行提取物进行预取时，并发送筛查对热带疾病的体外活性，包括疟疾，chagas疾病和利什曼病，以及细胞毒性测试以及细胞毒性测试 - 优先级级分级分数，以进一步的分析，基于生物赛的结果：在某种程度上表现出一定的分析，这些级数在某种程度上表现出了一定的影响，并在某种程度上表现出了其他分析，并在某种程度上表现出了其他分析，并在某种程度上表现出了其他分析。将继续进行进一步的分馏和复合隔离； SA 3，进行生物测定引导的分馏以分离和识别针对这些热带疾病作用的化合物。这些具体目标为这一国际研究科学家发展奖（IRSDA）提供了重点，涉及多年来在巴拿马洲际公会上合作的美国和外国导师，并为候选人的培训和指导制定了巨大的计划。