POTENTIAL ANTICANCER AGENTS FROM BASIDIOMYCETES

来自担子菌的潜在抗癌剂

• 批准号: 6293176
• 负责人: Esteban Edward Mena
• 金额: $ 10万
• 依托单位: LIFEPHARMS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-17 至 2002-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6293176
• 关键词: Ascomycetes; Basidiomycetes; DNA topoisomerases; X ray crystallography; antifungal agents; antineoplastics; bioassay; drug screening /evaluation; enzyme inhibitors; mass spectrometry; neoplasm /cancer pharmacology; nuclear magnetic resonance spectroscopy; telomerase

LifePharms, Inc. has established a collection of >12,000 unique species of basidiomycetes/ascomycetes, and the Natural Products Laboratory of Research Triangle Institute has a long and successful history of isolating potent antitumor agents from natural sources. By teaming our respective capabilities, we propose to 1) screen the LifePharms Inc., repository of basidiomycetes and ascomycetes for bioactivity against 9KB cells; 2) prioritize the samples based upon reconfirmation of activity, literature, availability of fungi, etc.; 3) obtain larger samples of the confirmed bioactive fungal species, 4) fractionate and purify the bioactive compounds from these larger samples using a bioassay guided approach; 5) characterize the pure bioactive compounds completely; 6) evaluate the bioactivity of the pure compounds in topoisomerase I inhibition and DNA nicking assays, as well as, measure EC50 values vs. 9KB cells; 7) scale up the isolation procedures in order to provide an ample quantity of pure compound for in vivo studies. Synthetic methodologies will be pursued for both total and analog synthesis of the bioactive compounds. (Phase II); 8) test the compounds for in vivo activity. (Phase II). PROPOSED COMMERCIAL APPLICATIONS: The National Cancer Institute estimated nearly 1.3 million new cases of cancer in 1998 and over one-half million deaths. Cancer has a mortality rate of about 160 deaths per 100,000 population, and the death rates are increasing at about 6% annually. The United States spends approximately $7-8 billion annually on pharmacological cancer therapies alone. For many forms of cancer, the 5-year survival rate is very low. Consequently, novel anticancer agents are needed urgently.

Lifepharms，Inc。已建立了> 12,000种独特的基本菌/comcycetes种类的集合，研究三角研究所的天然产品实验室拥有悠久而成功的历史，这些历史是将有效的抗肿瘤药与自然来源隔离开来。通过组合我们各自的功能，我们建议1）筛选Lifepharms Inc.，Basidiomycetes和commycetes的存储库，以实现对9KB细胞的生物活性； 2）根据重新确认活动，文献，真菌的可用性等确定样本的优先级； 3）获得确认的生物活性真菌物种的较大样品，4）使用生物测定指导方法从这些较大的样品中净化并净化生物活性化合物； 5）完全表征纯生物活性化合物； 6）评估拓扑异构酶I抑制和DNA缺口测定中纯化合物的生物活性，并测量EC50值与9KB细胞； 7）扩展隔离程序，以便为体内研究提供足够数量的纯化合物。对于生物活性化合物的总和模拟合成，将采用合成方法。 （第二阶段）; 8）测试体内活性的化合物。 （第二阶段）。拟议的商业应用：国家癌症研究所在1998年估计有近130万例新的癌症病例和超过一半的百万人死亡。癌症的死亡率约为每100,000人口约160人死亡，死亡率每年增加约6％。仅每年仅在药物癌症疗法上花费大约7-8亿美元。对于许多形式的癌症，5年的存活率非常低。因此，紧急需要新颖的抗癌剂。