TOPOISOMERASE II POISONING AND ANTICANCER DRUG DESIGN

拓扑异构酶 II 中毒和抗癌药物设计

• 批准号: 6691072
• 负责人: EMMANUEL A THEODORAKIS
• 金额: $ 19.84万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-02 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6691072
• 关键词: DNA gyrase; analog; antineoplastic antibiotics; cell line; chemical structure function; drug design /synthesis /production; enzyme inhibitors

Topoisomerases are nuclear enzymes that play an essential role in DNA metabolism and have emerged as the receptors for several clinically important anticancer agents. This proposal describes a research program directed toward the chemistry and biology of two classes of natural products that exhibit excellent antitumor activity by "poisoning" topoisomerase II. With a combination of bioorganic, computational and biological studies we aim to elucidate the mode of action of the above compounds and address issues pertaining to their structure-activity relationship. Research along these lines is expected to aid in the development of powerful and selective anticancer agents and could have important implications for cancer treatment.

拓扑异构酶是一种核酶，在DNA代谢中起着重要作用，并已成为几种临床重要抗癌药物的受体。该提案描述了一项针对两类天然产物的化学和生物学研究计划，这两类天然产物通过“中毒”拓扑异构酶II表现出出色的抗肿瘤活性。结合生物有机、计算和生物学研究，我们旨在阐明上述化合物的作用模式，并解决有关其构效关系的问题。沿着这些思路进行的研究有望有助于开发强大的、有选择性的抗癌药物，并可能对癌症治疗产生重要影响。