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.

海洋无脊椎动物长期以来一直被化学家确定为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，许多这些新型海洋产品以生物医学应用的方式改变了基本的生命过程。这些分子可以作为先导，指导制药和化学工业开发新产品。这项研究专门针对加勒比柳珊瑚作为一种可能的资源，新的抗结核病的天然产品。由于已知存在于加勒比海地区的柳珊瑚物种中，只有不到20%的物种的次级代谢物成分得到了化学评估，其中许多已被证明产生具有强效化疗特性的代谢物，因此该地区的柳珊瑚有可能含有丰富的新型药物。具体而言，在这项研究的四年中，我们计划仔细审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。用不同极性的溶剂（例如，己烷、二氯甲烷和甲醇）将使用抗结核活性测定进行监测。只有柳珊瑚提取物残留物具有很强的抗结核性质将进一步筛选化学结构特征的1H-和13 C-NMR光谱。如果筛选结果有必要，将通过色谱法（柱、GC、LC）进一步纯化并测定分子结构。结构解析将严重依赖于光谱方法（例如，1H和13 C NMR、MS、IR、UV）和X射线衍射技术。