TOPOISOMERASE II POISONING AND ANTICANCER DRUG DESIGN

拓扑异构酶是在DNA代谢中起重要作用的核酶，并且已经成为几种临床上重要的抗癌剂的受体。该建议描述了一个研究计划，针对两类天然产物的化学和生物学，通过“中毒”拓扑异构酶II表现出优异的抗肿瘤活性。结合生物有机，计算和生物学研究，我们的目标是阐明上述化合物的作用模式，并解决有关其结构-活性关系的问题。沿着这些路线的研究有望有助于开发强大的选择性抗癌药物，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.