2-[(ARYLMETHYL)AMINO]-2-METHYL-1,3-PROPANEDIOL DNA INTERCALATORS - AN EXAMINATION OF THE EFFECTS OF AROMATIC RING VARIATION ON ANTITUMOR-ACTIVITY AND DNA-BINDING

被引：58

作者：

BAIR, KW ^{[1
]}

ANDREWS, CW ^{[1
]}

TUTTLE, RL ^{[1
]}

KNICK, VC ^{[1
]}

CORY, M ^{[1
]}

MCKEE, DD ^{[1
]}

机构：

[1] BURROUGHS WELLCOME CO,DIV CELL BIOL,TUMOR BIOL SECT,RES TRIANGLE PK,NC 27709

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 07期

关键词：

D O I：

10.1021/jm00111a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The effects of variation of aromatic ring size, shape, and side-chain position on antitumor activity and DNA binding in a series of carbocyclic 2-[(arylmethyl)amino]-2-methyl-1,3-propanediols (AMAPs) were examined. In general, the interaction of AMAPs with DNA increases as the intercalating ring system grows in area, with three distinct binding levels evident. Isomers from a specific ring system appear to bind DNA similarly. DNA binding is not the sole criterion for antitumor activity for the AMAPs studied; the magnitude of the DELTA-T(m) does not correlate with the antitumor activity observed. Significant in vivo P388 activity was seen for AMAP congeners from several tetracyclic ring systems. However, isomers from each of the specific ring systems produced a wide range of in vivo P388 activity. Thus, AMAP antitumor activity is not a function of the ring system per se, but rather appears to be related to the shape of the specific molecule. Three AMAP congeners (crisnatol (770U82, 773U82, and 502U83) are currently in clinical trials.

引用

页码：1983 / 1990

页数：8

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