Anti-tuberculosis Agents from Gorgonian Octocorals

长期以来，化学家们一直认为海洋无脊椎动物可能是新的生物医药物质的来源。药理学家、生理学家和生化学家已经证明，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。这些分子可以作为引导制药和化学工业开发新产品的线索。本研究特别针对加勒比柳珊瑚作为一种新型抗结核天然产物的可能资源。由于加勒比地区已知存在的柳珊瑚物种中，只有不到20%的物种已被化学评估其次生代谢物组成，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具有含有丰富新药的潜力。具体地说，在这项研究的四年期间，我们计划仔细审查属于所有主要加勒比柳橙属的75个代表性物种的药理学和化学。不同极性溶剂（如己烷、二氯甲烷和甲醇）的初始萃取将使用抗结核活性测定法进行监测。通过1H- nmr和13C-NMR进一步筛选具有较强抗结核性的柳柑提取物残基的化学结构特征。如果筛选结果得到保证，将进行进一步的色谱纯化（柱、气相色谱、液相色谱）和分子结构测定。结构解析将主要依赖于光谱方法（例如，1H和13C NMR， MS， IR， UV）和x射线衍射技术。

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.