FLUORINATED COLCHICINOIDS - ANTITUBULIN AND CYTOTOXIC PROPERTIES

被引：31

作者：

RINGEL, I ^{[1
]}

JAFFE, D ^{[1
]}

ALERHAND, S ^{[1
]}

BOYE, O ^{[1
]}

MUZAFFAR, A ^{[1
]}

BROSSI, A ^{[1
]}

机构：

[1] NIDDK,NAT PROD SECT,BETHESDA,MD 20892

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 11期

关键词：

D O I：

10.1021/jm00115a026

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis of B-ring and C-ring trifluoroacetamide-substituted colchicinoids and fluoro-substituted colchicineethylamides is presented. The B-ring trifluoroacetamido-substituted analogues exhibit moderate enhancement of potency compared to the nonfluorinated analogues for tubulin assembly inhibition and cytotoxicity toward two wild type cell lines. The C-ring substituted fluoroethylamides have reduced relative potencies in the same systems due to the strong electron-withdrawing effect of the fluoro derivatives. The fluoro colchicinoids are much more cytotoxic toward drug-resistant cell lines than to the wild type cell lines. Their enhanced potency is probably due to an effect of the fluoro moiety on functions specific to resistant cells and/or their higher hydrophobicity that may result in higher intracellular drug content. This finding may suggest the application of designed fluorinated anticancer drugs to overcome acquired resistance which may develop after several regiments of treatment with a nonfluorinated chemotherapeutic agent.

引用

页码：3334 / 3338

页数：5

共 27 条

[1] CONFORMATIONAL STATES OF TUBULIN LIGANDED TO COLCHICINE, TROPOLONE METHYL-ETHER, AND PODOPHYLLOTOXIN [J].