MULTIMODAL ACTION OF ANTITUMOR AGENTS ON DNA - THE ELLIPTICINE SERIES
MULTIMODAL ACTION OF ANTITUMOR AGENTS ON DNA - THE ELLIPTICINE SERIES
复制标题
DOI：
10.1016/0003-9861(87)90463-2
复制
发表时间：
1987-11-15
影响因子：
3.9
通讯作者：
AUCLAIR, C
中科院分区：
文献类型：
--
作者：
AUCLAIR, C
大多数细胞毒性抗癌剂直接或间接与核DNA相互作用，核DNA是这类化合物的最终靶点。对于一种特定类型的药物，DNA水平上的直接和间接作用通常都会造成各种类型的干扰或损害。这种多模式的作用机制被椭圆素类抗肿瘤药物很好地解释了，这些抗肿瘤药物可能通过嵌入与DNA结合，可能发生共价结合，可能产生氧化物种，并可能干扰拓扑异构酶II的催化活性。因此，这些化合物的抗肿瘤活性可能是通过交替的细胞毒事件产生的。本文综述了椭圆碱类化合物对DNA作用的性质与其细胞毒和/或抗肿瘤活性之间的关系。拓扑异构酶介导的DNA裂解的发生似乎与抗肿瘤活性有关。药物干扰拓扑异构酶II作用的能力需要在其结构上存在一个可氧化的酚基。作用于这种酶的所有抗肿瘤药物都有这一特征(或相关特征)。
Most cytotoxic anticancer agents interact directly or indirectly with nuclear DNA, the ultimate target for this class of compounds. For a given type of drug both direct and indirect action at the DNA level usually causes various types of interference or damage. This mutimodal mechanism of action is well illustrated by antitumor drugs in the ellipticine series which may bind to DNA through intercalation, may undergo covalent binding, may generate oxidizing species, and may interfere with the catalytic activity of topoisomerase II. The antitumor activity of these compounds may, therefore, result from alternative cytotoxic events. The present review summarizes information obtained with ellipticine compounds on the relation between the nature of the drugs' action on DNA and their cytotoxic and/or antitumor activity. The occurrence of topoisomerase-mediated DNA cleavage appears to be responsible for antitumor activity. The capability of the drugs to interfere with the action of topoisomerase II requires the presence of an oxidizable phenolic group on their structure. This feature (or a related one) is shared by all antitumor drugs acting on this enzyme.