Isothiazole dioxides:: Synthesis and inhibition of Trypanosoma brucei protein farnesyltransferase

被引：22

作者：

Clerici, F

Gelmi, ML

Yokoyama, K

Pocar, D

Van Voorhis, WC

Buckner, FS

Gelb, MH

机构：

[1] Univ Milan, Fac Farm, Ist Chim Organ, I-20133 Milan, Italy

[2] Univ Washington, Dept Chem, Seattle, WA 98195 USA

[3] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[4] Univ Washington, Dept Med, Seattle, WA 98195 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 16期

关键词：

D O I：

10.1016/S0960-894X(02)00338-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of isothiazole dioxides was synthesized and evaluated as inhibitors of protein farnesyltransferase from the parasite that causes African sleeping sickness (Trypanosoma brucei). The most potent compound in the series inhibited the parasite enzyme with an IC50 of 2 muM and blocked the growth of the bloodstream parasite in vitro with an ED50 of 10 muM. The same compound inhibited rat protein farnesyltransferase and protein geranylgeranyltransferase type I only at much higher concentration. (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：2217 / 2220

页数：4

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