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学物质的来源。药理学家、生理学家和生物化学家已经证明，这些新型海洋产品中的许多都以生物医学应用的方式改变了基本的生命过程。这些分子可以作为指导制药和化工行业开发新产品的线索。这项研究专门针对加勒比海柳珊瑚，将其作为新型抗结核病天然产品的可能来源。由于在加勒比地区已知的柳珊瑚物种中，只有不到20%的物种对其次生代谢物成分进行了化学评估，其中许多物种已被证明产生具有强大化学治疗特性的代谢物，该地区的柳珊瑚可能含有丰富的新药。具体地说，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海柳珊瑚属的75个代表性物种的药理和化学。使用不同极性的溶剂(如己烷、二氯甲烷和甲醇)的初始提取将通过抗结核活性分析进行监测。只有具有较强抗结核特性的柳珊瑚提取物残留物将通过1H-和13C-核磁共振波谱进一步筛选化学结构特征。如果筛选结果有保证，将进行进一步的层析(柱、GC、LC)纯化和分子结构测定。结构鉴定将在很大程度上依赖于波谱方法(如1H和13C核磁共振、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.