ISOLATION OF NOVEL MECHANISM-BASED ANTITUMOR AGENTS

基于新机制的抗肿瘤药物的分离

• 批准号: 6352740
• 负责人: DAVID GEORGE IAN KINGSTON
• 金额: $ 14.83万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6352740
• 关键词: DNA damage; DNA topoisomerases; Saccharomyces cerevisiae; X ray crystallography; antineoplastics; bioassay; biological products; chemical structure function; chromatography; drug screening /evaluation; enzyme inhibitors; stereochemistry

The overall objective of the proposed research is to discover new natural products with significant clinically useful anticancer activity. The specific aims of the program are: 1. To acquire 20-40 extracts per year which show good in vitro activity in topoisomerase I inhibition, topoisomerase II inhibition, or DNA damaging bioassays, The active extracts will come wither from preliminary screening carried out at the University of Virginia as part of the core activities of this Group, preliminary screening carried out at SmithKline Beecham Pharmaceuticals, or from screening carried out by us in collaboration with various colleagues around the world. 2. To fractionate each of the active extracts using a bioassay-directed fractionation scheme, and to isolate pure active compounds with selective activity in one of the bioassays indicated. 3. To determine the structures of all active compounds by whichever combination of chemical manipulation, spectroscopic techniques,a nd X-ray crystallography proves most appropriate to the specific problem. 4. To reisolate adequate amounts of all active compounds for further biological evaluation by Laboratory Program 1 (SmithKline Beecham Parmaceuticals). 5. To collaborate with Laboratory Program 4 (Dr. Sundberg, University of Virginia) in the design and synthesis of appropriate analogs of newly isolated active compounds. 6. To collaborate with other members of the Group as appropriate to assist in the development of active compounds as clinical candidates.

拟议研究的总体目标是发现新的自然资源