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：
7762064
负责人：
Abimael D Rodriguez
金额：
$ 30.94万
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/7762064
关键词：
AIDS/HIV problem Accounting Affinity Animals Anti-Infective Agents Antimalarials Aplysia Arts 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 Epidemiology Figs - dietary Funding Growth Inhibitors Healthcare Hexanes 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 Pharmacologic Substance 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

AIDS/HIV problem Accounting Affinity Animals Anti-Infective Agents Antimalarials Aplysia Arts 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 Epidemiology Figs - dietary Funding Growth Inhibitors Healthcare Hexanes 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 Pharmacologic Substance 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

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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）：这项研究冒险旨在探索波多黎各海洋生物多样性，作为发现新的和改善的抗癌和抗菌药物候选者的一种手段，并进一步寻求将这些候选药物培养为商业上可接受的治疗疗法，并能够管理和治疗Cancers and Canseases and Chare Care，并促成了综合疗法，并撰写了综合疗法。海洋无脊椎动物已被发现很长时间以来可能是新生物医学物质的来源。药理学家，生理学家和生物化学家已经证明，其中许多新型海洋产品以暗示生物医学应用的方式修改了基本生命过程。这些分子可以用作指导开发新产品的药物和化学工业的铅。我们提出的研究专门针对波多黎各海洋无脊椎动物（海绵，戈尔戈尼珊瑚，软体动物和阿西迪亚人），是新型抗癌和抗巨质天然产物的可能资源。由于已知在波多黎各附近存在的海洋无脊椎动物中只有不到1％的物种已通过化学评估其继发代谢物组成，因此已证明其中许多人可产生具有有效的化学治疗特性的代谢物，因此该地区的生物体有可能含有新型药物的财富。具体而言，在这项研究的四年中，我们计划仔细仔细检查350种属于四个主要加勒比海门的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法监测具有不同极性（例如己烷，甲基氯化物和甲醇）的溶剂的初始提取。只有HPLC/ESI-MS和NMR光谱学进一步筛选具有强大细胞毒性和抗微生物特性的提取物残留物。如果通过筛选结果保证，将通过色谱法（列，GC，LC）进行进一步纯化，并确定分子结构。结构阐明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。候选化合物将安排用于临床试验以评估其临床潜力。通过确定产生这些化合物的化学结构以及最终的生化途径以及控制其生产的环境或生理触发因素，可以开发出增强商业生产的技术。公共卫生相关性：仅在美国，预计将在2008年诊断出超过140万个新的癌症病例。当前的流行病学证据表明，每年的艾滋病毒/艾滋病，疟疾和结核病占全球超过900万人死亡。我们的研究计划旨在探索海洋无脊椎动物生物多样性，以此作为发现新的和改善的抗癌和抗感染药物候选者的一种手段，并进一步寻求将这些候选药物发展为商业上可接受的治疗剂，并具有管理和治疗这些疾病的能力，从而有助于全球医疗保健。