SYNTHESIS AND ANTITUMOR-ACTIVITY OF TROPOLONE DERIVATIVES .7. BISTROPOLONES CONTAINING CONNECTING METHYLENE CHAINS

被引：47

作者：

YAMATO, M ^{[1
]}

ANDO, J ^{[1
]}

SAKAKI, K ^{[1
]}

HASHIGAKI, K ^{[1
]}

WATAYA, Y ^{[1
]}

TSUKAGOSHI, S ^{[1
]}

TASHIRO, T ^{[1
]}

TSURUO, T ^{[1
]}

机构：

[1] CANC CHEMOTHERAPY CTR,TOSHIMA KU,TOKYO 170,JAPAN

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 02期

关键词：

D O I：

10.1021/jm00080a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Bistropolone derivatives (4-12) containing differing lengths of linkage between the two tropolone rings were prepared and examined for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. Parent compound 3, related compounds previously prepared, and the new compounds 4-12 were evaluated for inhibitory activity against ribonucleotide reductase by indirect means to measure their effects on the dNTP pool imbalance. Present structure-activity relationship results would suggest that potently active bistropolones in vivo inhibit intracellular ribonucleotide reductase through chelating with the two irons at the two active sites of the enzyme.

引用

页码：267 / 273

页数：7

共 20 条

[1] SELECTION OF MAMMALIAN THYMIDINE AUXOTROPHIC CELL MUTANTS DEFECTIVE IN THYMIDYLATE SYNTHASE BY THEIR REDUCED SENSITIVITY TO METHOTREXATE [J].