Synthesis, conformation, and biological activity of teleocidin mimics, benzolactams. A clarification of the conformational flexibility problem in structure-activity studies of teleocidins

被引：114

作者：

Endo, Y ^{[1
]}

Ohno, M ^{[1
]}

Hirano, M ^{[1
]}

Itai, A ^{[1
]}

Shudo, K ^{[1
]}

机构：

[1] INST MED MOLEC DESIGN,BUNKYO KU,TOKYO 113,JAPAN

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 1996年 / 118卷 / 08期

关键词：

D O I：

10.1021/ja953578v

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Tumor-promoter teleocidins and their active congeners (indolactams) are known to exist in an equilibrium between at least two conformational states in solution, the twist and sofa form, due to cis-trans isomerization of the amide bond and the steric effects of substituents on the nine-membered lactam ring. Benzolactam-Vs, in which the indole ring of indolactams is replaced with a benzene ring, were designed and synthesized in an attempt to reproduce the active conformation of teleocidins. Among these benzolactams, eight-membered lactams (benzolactam-V8) can only exist in the twist form, and 9- and 10-membered lactams (benzolactam-V9 and -V10) exist exclusively in the sofa form in solution. The stronger biological activity of benzolactam-V-8-310 than that of indolactam-V (IL-V) and the inactivity of benzolactam-V-9-310 for differentiation inducing activity of HL-60 clearly indicated that the twist form is close to the active conformation of teleocidins.

引用

页码：1841 / 1855

页数：15

共 42 条

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