(1-PYRENYLMETHYL)AMINO ALCOHOLS, A NEW CLASS OF ANTITUMOR DNA INTERCALATORS - DISCOVERY AND INITIAL AMINE SIDE-CHAIN STRUCTURE ACTIVITY STUDIES
(1-PYRENYLMETHYL)AMINO ALCOHOLS, A NEW CLASS OF ANTITUMOR DNA INTERCALATORS - DISCOVERY AND INITIAL AMINE SIDE-CHAIN STRUCTURE ACTIVITY STUDIES
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DOI：
10.1021/jm00171a012
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发表时间：
1990-09-01
影响因子：
7.3
通讯作者：
MCKEE, DD
中科院分区：
文献类型：
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作者：
BAIR, KW;TUTTLE, RL;MCKEE, DD
在这项工作中研究的一系列 1-芘基甲胺中，研究了其结构、与 DNA 的相互作用以及小鼠抗肿瘤活性之间的关系。结合研究表明，所有这些 1-芘基甲胺衍生物都通过嵌入在一定程度上与 DNA 结合。侧链中额外碱性胺基的存在增强了由于静电相互作用而产生的 DNA 结合。那些仅含有单一碱性苄胺的化合物与 DNA 的结合类似。只有庞大侧链的存在似乎会减少所检测化合物中的 DNA 相互作用。尽管(1-芘基甲基)氨基醇具有抗肿瘤活性，但该系列中有用的抗肿瘤活性仅限于那些带有2-氨基-1,3-丙二醇型侧链的同系物。这些衍生物与 DNA 适度结合。 DNA 结合是该系列中抗肿瘤活性的必要但不充分的标准。此外，DNA结合的强度与活性化合物组中的抗肿瘤活性不相关。三种相关的 2-[(芳甲基)氨基]-1,3-丙二醇衍生物 (AMAP) [crisnatol (770U82)、773U82 和 502U83] 目前作为潜在的抗肿瘤药物正在进行临床试验。
In the series of 1-pyrenylmethylamines studied in this work the relationships among structure, interaction with DNA, and murine antitumor activity were examined. Binding studies show that all of these 1-pyrenylmethylamine derivatives bind to some extent to DNA by intercalation. The presence of additional basic amine groups in the side chain enhances DNA binding due to electrostatic interactions. Those compounds containing only a single basic benzylic amine bind similarly to DNA. Only the presence of bulky side chains appears to decrease the DNA interactions in the compounds examined. Although antitumor activity is seen for (1-pyrenylmethyl)amino alcohols, useful antitumor activity in the series is limited to those congeners bearing the 2-amino-1,3-propanediol-type side chain. These derivatives bind moderately to DNA. DNA binding is a necessary but not sufficient criterion for antitumor activity in the series. In addition, the strength of DNA binding does not correlate with the antitumor activity in the group of active compounds. Three related 2-[(arylmethyl)amino]-1,3-propanediol derivatives (AMAPs) [crisnatol (770U82), 773U82, and 502U83] are currently in clinical trials as potential antitumor agents.