Anti-tuberculosis Agents from Gorgonian Octocorals

柳珊瑚八珊瑚的抗结核剂

• 批准号: 6766444
• 负责人: ABIMAEL D RODRIGUEZ
• 金额: $ 10.82万
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6766444
• 关键词: Caribbean; Puerto Rico; X ray crystallography; animal extract; antibacterial agents; bioassay; biotechnology; biotherapeutic agent; cell growth regulation; chemical structure function; communicable disease control; coral; cytotoxicity; diterpenes; drug discovery /isolation; drug screening /evaluation; emerging infectious disease; inhibitor /antagonist; mass spectrometry; metabolism; nuclear magnetic resonance spectroscopy; pharmacology; solvent extraction; systematic biology; tuberculosis

Marine invertebrates have been identified for a long time by chemists 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. This research aims specifically at Caribbean gorgonian octocorals as a likely resource for novel anti-tuberculosis natural products. Since less than 20% of the species of gorgonian octocorals known to exist in the Caribbean region have been assessed chemically for their secondary metabolite composition, and many of these have been shown to produce metabolites possessing potent chemotherapeutic properties, gorgonians 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 75 representative species belonging to all the major Caribbean gorgonian genera. Initial extraction with solvents of different polarities (e.g., hexane, methylene chloride, and methanol) will be monitored using anti-tuberculosis activity assays. Only gorgonian extract residues possessing strong anti-tuberculosis properties will be screened further for chemical structural features by 1H- and 13C-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.

化学家长期以来一直认为海洋无脊椎动物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。这项研究特别针对加勒比柳珊瑚八珊瑚作为新型抗结核天然产品的可能资源。由于已知存在于加勒比地区的柳珊瑚种类中，只有不到 20% 的次生代谢物成分经过化学评估，并且其中许多已被证明能产生具有有效化疗特性的代谢物，因此来自该地区的柳珊瑚具有潜在的潜力。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所有主要加勒比柳珊瑚属的 75 种代表性物种的药理学和化学。使用不同极性溶剂（例如己烷、二氯甲烷和甲醇）的初始提取将使用抗结核活性测定进行监测。只有具有强抗结核特性的柳珊瑚提取物残留物才会通过 1H 和 13C-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。