TOPOISOMERASE II POISONING AND ANTICANCER DRUG DESIGN

拓扑异构酶是一种核酶，在DNA代谢中起着至关重要的作用，并已成为几种临床上重要的抗癌药物的受体。这项建议描述了一项针对两类通过“毒化”拓扑异构酶II表现出优异抗肿瘤活性的天然产物的化学和生物学研究计划。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，并解决与它们的构效关系有关的问题。沿着这些思路进行的研究有望帮助开发有效和选择性的抗癌药物，并可能对癌症治疗产生重要影响。

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.