NOVEL STRATEGIES FOR PLANT-DERIVED ANTICANCER AGENTS

植物源抗癌药物的新策略

• 批准号: 3549682
• 负责人: Geoffrey A Cordell
• 金额: $ 85.28万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3549682
• 关键词: antineoplastics; cooperative study; drug design /synthesis /production; plant extracts

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.

伊利诺伊大学芝加哥分校财团(UIC)， 三角研究院(RTI)和葛兰素史克集团研究有限公司(GSK) 结合了他们在与世隔绝和结构上的丰富经验 阐明具有生物活性的天然产物以开发一种 整合、集成的计划，用于隔离新的、有选择的 有可能发展为癌症的抗癌药物 化疗药物。 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知名植物学家， 根据它们的地方性，它们在当地用于治疗癌症， 寄生虫病或传染病，或基于进程，使用 UIC的NAPRALERT数据库，上面显示了植物排名 在实验上具有某种形式的抗癌活性，为此 主动原则未知。 通过这一新的收集策略获得的植物将是 在UIC或RTI使用相同的技术提取，以负担 两个组分，将在一组25个检测中进行评估，基于 细胞毒性、机制和肿瘤生长相关的不同途径 目前在UIC、RTI和葛兰素史克建立和运行的检测方法。数据 将对这些化验结果进行详细存储和分析，以便优先 用于回收和分馏的植物清单可由一个 评估小组。此组将具有完全访问权限以完成 对有问题的植物进行计算机文献调查，以便 对于已知的活性化合物的去重复可以尽可能地有意义。 将采用生物测定指导的分级程序(在UIC，RTI 和葛兰素史克)，用于采购纯活性原则，这将是 具有结构特征的。如此发现的新颖的活性化合物将 将在我们的生物检测电池中进行进一步评估。根据这些数据和 分离物的结构，将决定是否进一步 潜在用作化疗药物的试剂的开发。 这些更高级的生物和毒理学测试阶段也是如此 因为合成或分离更多的铅化合物将是 由葛兰素史克赞助。 该联盟欢迎NCI工作人员在整个 发现进程，并计划定期举行关键科学会议 所有三个地点的工作人员，以加强持续的沟通， 信息交流和决策过程。太棒了 分离、结构确定、化学修饰、 合成以及体外和体内生物学评价可在以下网址获得： 进行这项工作的联合体场地。