NOVEL STRATEGIES FOR PLANT-DERIVED ANTICANCER AGENTS

伊利诺伊大学芝加哥分校（UIC）的联盟小组， 三角研究所（RTI）和葛兰素集团研究有限公司（葛兰素） 结合了他们在隔离和结构方面的丰富经验 生物活性天然产物的阐明， 巩固的，综合方案的分离新的，选择性的， 具有发展为癌症的潜力的抗癌剂 化疗剂。 用于分析的植物材料（每年500份）将由 主要分布在热带国家的植物学家， 它们的地方性，它们在当地用于治疗癌症， 寄生虫或传染病，或基于一个过程，使用 UIC的NAPRALERT数据库，对先前显示的植物进行排名 在实验上具有某种形式的抗癌活性， 活性成分未知。 由于这种新的收集策略而获得的植物将被 在UIC或RTI提取，使用相同的技术， 将在一组25次测定中评价的两个组分， 细胞毒性、基于机制和肿瘤生长相关的多种方法 目前在UIC、RTI和Glaxo建立和运行的检测方法。 数据 将被储存和详细分析， 用于再收集和分馏的植物的列表可以由 评估小组。 该组将拥有完全访问权限， 计算机化的植物文献调查， 已知活性化合物的去复制可以尽可能有意义。 将采用生物测定指导的分级分离程序（在UIC、RTI 和葛兰素）采购纯活性成分，这将是 结构特点。 由此发现的新型活性化合物将 在我们的生物检测中做进一步评估 基于这些数据和 隔离物的结构，将决定进一步 开发该试剂作为化疗剂的潜在用途。 这些生物学和毒理学测试的更高级阶段，以及 因为大量先导化合物的合成或分离将 由Glaxo赞助。 该联盟欢迎NCI工作人员参与整个 发现过程，并计划定期举行会议的关键科学 所有三个地点都有工作人员，以加强持续的沟通， 信息交流和决策进程。 优秀 用于分离、结构测定、化学改性、 合成以及体外和体内生物学评价可在 进行这项工作的联合体网站。

The Consortium Group of the University of Illinois at Chicago (UIC), Research Triangle Institute (RTI) and Glaxo Group Research Ltd. (Glaxo) have combined their vast experience in the isolation and structure elucidation of biologically active natural products to develop a consolidated, integrated program for the isolation of novel, selective anticancer agents which will have the potential for development as cancer chemotherapeutic agents. Plant materials for analysis (500 per year) will be collected by established botanists located primarily in tropical countries, either on the basis of their endemic nature, their local use for treating cancer, parasitic or infectious diseases, or based on a process, using the NAPRALERT database at UIC, of ranking plants previously shown experimentally to have some form of anticancer activity and for which the active principle is not known. Plants acquired as a result of this novel collection strategy will be extracted either at UIC or at RTI, using identical techniques, to afford two fractions which will be evaluated in a battery of 25 assays based on a diverse approach of cytotoxicity, mechanism-based and tumor growth related assays currently established and operational at UIC, RTI and Glaxo. Data from these assays will be stored and analyzed in detail so that a priority list of plants for recollection and fractionation can be formulated by an evaluation panel. This group will have full access to complete computerized literature surveys of the plants in question so that dereplication for known active compounds can be as meaningful as possible. Bioassay-directed fractionation procedures will be employed (at UIC, RTI and Glaxo) for the procurement of pure active principles, which will be structurally characterized. Novel, active compounds thus discovered will be further evaluated in our battery of bioassays. Based on these data and the structure of the isolate, a decision will be made regarding further development of the agent for potential use as a chemotherapeutic agent. These more advanced stages of biological and toxicological testing, as well as synthesis or isolation of larger quantities of lead compounds will be sponsored by Glaxo. The Consortium welcomes the involvement of NCI staff throughout the discovery process, and plans to hold regular meetings of the key scientific personnel at all three sites in order to enhance ongoing communication, exchanges of information and decision-making processes. Excellent facilities for isolation, structure determination, chemical modification, synthesis and in vitro and in vivo biological evaluation are available at the consortial sites for the conduct of this work.