Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase

被引：40

作者：

Cavalli, Andrea ^{[1
,2
]}

Lizzi, Federica ^{[1
]}

Bongarzone, Salvatore ^{[1
]}

Brun, Reto ^{[3
]}

Krauth-Siegel, R. Luise ^{[4
]}

Bolognesi, Maria Laura ^{[1
]}

机构：

[1] Alma Mater Studiorum Univ Bologna, Dept Pharmaceut Sci, I-40126 Bologna, Italy

[2] IIT, Dept Drug Discovery & Dev, I-16163 Genoa, Italy

[3] Swiss Trop Inst, CH-4002 Basel, Switzerland

[4] Biochem Zentrum Univ Heidelberg, D-69120 Heidelberg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 11期

关键词：

Neglected tropical disease; Trypanosoma; Leishmania; Leishmaniasis; Trypanosomiasis; Docking simulations; ANTIPARASITIC DRUG DISCOVERY; TRYPANOSOMA-CRUZI; PARASITIC DISEASES; CHAGAS-DISEASE; ANTAGONISTS; MALARIA; DESIGN; PRAZOSIN; TARGETS;

D O I：

10.1016/j.bmcl.2009.04.060

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel quinazoline-type compounds were designed as inhibitors of the parasite specific enzyme trypanothione reductase (TR), and their biological activities were evaluated. Some of our compounds inhibited TR, showed selectivity for TR over human glutathione reductase, and inhibited parasite growth in vitro. We propose that the quinazoline framework is a privileged structure that can be purposely modified to design novel TR inhibitors. Furthermore, the use of privileged motifs might emerge as an innovative approach to antiparasitic lead candidates. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3031 / 3035

页数：5

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