New Leads Against Cancer and Infectious Diseases from Puerto Rican Reef Species

波多黎各珊瑚礁物种对抗癌症和传染病的新线索

基本信息

批准号：
8035369
负责人：
Abimael D Rodriguez
金额：
$ 29.5万
依托单位：
UNIVERSITY OF PUERTO RICO RIO PIEDRAS
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8035369
关键词：
AIDS/HIV problem Accounting Affinity Animals Anti-Infective Agents Antimalarials Aplysia Biochemical Pathway Biodiversity Biological Biological Assay Biological Factors Biomedical Research Caribbean region Cells Cessation of life Chemical Industry Chemical Structure Chemicals Chemistry Clinical Clinical Trials Collection Column Chromatography Communicable Diseases Crude Extracts Diagnosis Disease Drug Industry Epidemiology Funding Growth Inhibitors Healthcare Hexanes High Pressure Liquid Chromatography Infection Inhibitory Concentration 50 Investigation Lead Life Location Malaria Malignant Neoplasms Marine Invertebrates Marines Methanol Methods Methylene Chloride Molecular Structure Monitor Mycobacterium tuberculosis NMR Spectroscopy Organism Parents Pharmaceutical Preparations Pharmacology Physiological Plasmodium Plasmodium falciparum Porifera Predatory Behavior Process Production Property Proteins Proteomics Puerto Rican Puerto Rico Research Resources Schedule Screening Result Screening procedure Solvents Source Structure System Techniques Therapeutic Time Tuberculosis Urochordata X ray diffraction analysis X-Ray Diffraction antimicrobial antimicrobial drug ascidian cancer cell coral cytotoxic cytotoxicity drug candidate genome sequencing global health improved marine organism neoplastic cell novel preclinical study programs public health relevance small molecule therapeutic target

项目摘要

DESCRIPTION (provided by applicant): This research venture aims to explore Puerto Rican marine biodiversity as a means to discover new and improved anti-cancer and anti-microbial drug candidates, and further seeks to develop these drug candidates into commercially acceptable therapeutics, with the capacity to manage and treat cancers as well as infectious diseases, and contribute to global health care. Marine invertebrates have been identified for a long time as likely sources of new biomedicinal substances. Pharmacologists, physiologists and biochemists have demonstrated that many of these novel marine products modify fundamental life processes in ways suggesting biomedical applications. These molecules can serve as leads to guide the pharmaceutical and chemical industries in developing new products. Our proposed research aims specifically at Puerto Rican marine invertebrates (sponges, gorgonian corals, mollusks, and ascidians) as a likely resource for novel anti- cancer and anti-microbial natural products. Since less than 1% of the species of marine invertebrates known to exist near Puerto Rico have been assessed chemically for their secondary metabolite composition, and many of these have been shown to produce metabolites possessing potent chemotherapeutic properties, organisms from this region have the potential to contain a wealth of novel drugs. Specifically, during the four years of this research we plan to carefully scrutinize the pharmacology and chemistry of 350 representative species belonging to four major Caribbean phyla. Initial extraction with solvents of different polarities (e.g., hexane, methylene chloride, and methanol) will be monitored using cytotoxicity and anti-microbial activity assays. Only extract residues possessing strong cytotoxic and anti-microbial properties will be screened further for chemical structural features by HPLC/ESI-MS and NMR spectroscopy. Further purification by chromatography (column, GC, LC) and determination of molecular structure will proceed if warranted by the screening results. Structure elucidation will rely heavily on spectral methods (e.g., 1H and 13C NMR, MS, IR, UV) and X-ray diffraction techniques. Candidate compounds will be scheduled for clinical trial to assess their clinical potential. By determining the chemical structures and, eventually, the biochemical pathways by which these compounds are produced and the environmental or physiological triggers controlling their production, techniques of enhanced commercial production can be developed. PUBLIC HEALTH RELEVANCE: In the USA alone over 1.4 million new cancer cases are expected to be diagnosed in 2008. Current epidemiological evidence suggests that every year HIV/AIDS, malaria, and tuberculosis account for over 9 million deaths worldwide. Our research program aims to explore marine invertebrate biodiversity as a means to discover new and improved anti-cancer and anti-infective drug candidates, and further seeks to develop these drug candidates into commercially acceptable therapeutics, with the capacity to manage and treat these diseases, thus contributing to global health care.

描述（由申请人提供）：该研究项目旨在探索波多黎各海洋生物多样性，作为发现新的和改进的抗癌和抗微生物候选药物的手段，并进一步寻求将这些候选药物开发成商业上可接受的治疗方法，管理和治疗癌症以及传染病的能力，并为全球卫生保健做出贡献。长期以来，海洋无脊椎动物已被认为是新生物医学物质的可能来源。药理学家、生理学家和生物化学家已经证明，许多新颖的海洋产品以生物医学应用的方式改变基本的生命过程。这些分子可以作为指导制药和化学工业开发新产品的线索。我们提出的研究专门针对波多黎各海洋无脊椎动物（海绵、柳珊瑚、软体动物和海鞘），作为新型抗癌和抗微生物天然产品的可能资源。由于已知存在于波多黎各附近的海洋无脊椎动物物种中，只有不到 1% 对其次生代谢物成分进行了化学评估，并且其中许多已被证明能够产生具有有效化疗特性的代谢物，因此来自该地区的生物体有潜力含有丰富的新型药物。具体来说，在这项研究的四年中，我们计划仔细检查属于加勒比四大门的 350 种代表性物种的药理学和化学。将使用细胞毒性和抗微生物活性测定来监测使用不同极性溶剂（例如己烷、二氯甲烷和甲醇）的初始提取。只有具有强细胞毒性和抗微生物特性的提取物残留物才会通过 HPLC/ESI-MS 和 NMR 光谱进一步筛选其化学结构特征。如果筛选结果有保证，将通过色谱法（柱、GC、LC）进一步纯化并确定分子结构。结构解析将在很大程度上依赖于光谱方法（例如 1H 和 13C NMR、MS、IR、UV）和 X 射线衍射技术。候选化合物将安排进行临床试验，以评估其临床潜力。通过确定化学结构，最终确定这些化合物产生的生化途径以及控制其产生的环境或生理触发因素，可以开发增强商业生产的技术。公共健康相关性：仅在美国，2008 年预计将诊断出超过 140 万新癌症病例。目前的流行病学证据表明，每年全世界有超过 900 万人死于艾滋病毒/艾滋病、疟疾和结核病。我们的研究计划旨在探索海洋无脊椎动物的生物多样性，作为发现新的和改进的抗癌和抗感染候选药物的手段，并进一步寻求将这些候选药物开发成商业上可接受的疗法，具有管理和治疗这些疾病的能力，从而为全球卫生保健做出贡献。