ANTINEOPLASTIC AGENTS FROM MARINE MICROALGAE

这项建议的战略是开发和使用创新 基于对肿瘤生物学和分子生物学的新理解的方法 了解癌症，发现有效的化疗药物 治疗乳腺、前列腺、卵巢、肺、结肠等实体肿瘤。这个 我们NCNPDDG项目的这个实验室计划的目标是使用 从野外采集的海洋中发现新的先导化合物的方法 蓝藻和大型藻类以及养殖的海洋微藻。 这项研究的长期目标是使用创新的生物化学 以及基于细胞的分析，以发现和描述结构新颖的天然 作为抗癌先导化合物的产品来自海洋大型藻类和 微藻。 这项工作的具体目标是：1)评估大约1000- 1200种不同领域采集或培养的海洋微生物和 大型藻类在5年内进行了一系列创新的生化 和Sandoz制药公司提供的基于细胞的分析，2)到 上述筛选工作的分级活性提取物如下 生物化学或细胞分析的活性，如 适当的，以获得有潜力的纯天然产品 抗癌先导，3)阐明纯活性化合物的结构 使用光谱化学技术，4)继续放大培养 活跃物种或丛生或大型藻类物种的重新采集 并重新分离活性化合物，为药理研究提供样品 和临床研究，5)生产半合成类似物 活性化合物在构效关系研究中的应用 新的先导化合物，以及6)获得有前景的专利覆盖 抗肿瘤天然产物及其衍生物。 热带海洋微藻的采集方法 来自热带和温带地区的大型藻类将使用 我们实验室使用的浅水油田采集技术。 水和脂肪提取物将在创新的生物化学中进行评估 和我们在Sandoz的合作者进行的基于细胞的分析。隔离 活性化合物之后将进行生化分析，并 偏重于二维原子核的光谱化学方法 磁共振将被用来解决新的 抗癌先导化合物。回忆或重新培养将提供 用于深入生化和体内研究的新型癌症先导化合物样品 评估。

The strategy of this proposal is to develop and use innovative approaches, based on new understanding of tumor biology and the molecular understanding of cancer, to discover chemotherapeutics effective in treating solid tumors of the breast, prostate, ovary, lung and colon. The goal of this laboratory program of our NCNPDDG project will be to use these assays to discover new lead compounds from field collected marine cyanobacteria and macroalgae as well as cultured marine microalgae. The long term objective of this research is to use innovative biochemical and cell-based assays to discover and describe structurally-novel natural products as anticancer lead compounds from marine macroalgae and microalgae. The specific aims of this work are to: 1) to evaluate approximately 1000- 1200 extracts of various field collected or cultured marine micro- and macro-algae over a 5 year period in a series of innovative biochemical and cell-based assays available at Sandoz Pharmaceutical, 2) to fractionate active extracts from the above screening efforts, following activity with either the biochemical or cell-based assays, as appropriate, to obtain pure natural products which are potential anticancer leads, 3) to elucidate the structures of pure active compounds using spectrochemical techniques, 4) to continue the scaled-up culture of active species or re-collection of tuft-forming or macroalgal species and re-isolation of active compounds to provide samples for pharmacologic and clinical investigation, 5) to produce semi-synthetic analogs of active compounds for exploration of structure-activity relationships in new lead compounds, and 6) to obtain patent coverage on promising antitumor natural products and their derivatives. The methodologies for collection of marine microalgae from the tropics and macroalgae from the tropics as Well as temperate locations will use shallow water field collection techniques in use in our laboratory. Aqueous and lipid extracts will be evaluated in innovative biochemical and cell based assays with our collaborators at Sandoz. Isolation of the active compounds will be followed with the biochemical assays, and a palate of spectrochemical methods emphasizing two-dimensional nuclear magnetic resonance will be used to solve the structures of the new anticancer lead compounds. Recollections or recultures will provide samples of new cancer lead compounds for in-depth biochemical and in vivo evaluations.