Synthesis and biological evaluation of thiazolidine-2-one 1,1-dioxide as inhibitors of Escherichia coli β-ketoacyl-ACP-synthase III (FabH)

被引：35

作者：

Alhamadsheh, Mamoun M.

Waters, Norman C.

Huddler, Donald P.

Kreishman-Deitrick, Mara

Florova, Galina

Reynolds, Kevin A. ^{[1
]}

机构：

[1] Portland State Univ, Dept Chem, Portland, OR 97207 USA

[2] Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 04期

关键词：

FabH; fatty acid biosynthesis; inhibition; SAR; antimalarial;

D O I：

10.1016/j.bmcl.2006.11.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

A series of cyclic sulfones has been synthesized and their activity against beta-ketoacyl-ACP-synthase III (FabH) has been investigated. The compounds are selectively active against Escherichia coli FabH (ecFabH), but not Mycobacterium tuberculosis FabH (mtFabH) or Plasmodium falciparum KASIII (PfKASIII). The activity against ecFabH ranges from 0.9 to > 100 mu M and follows a consistent general SAR trend. Many of the compounds were shown to have antimalarial activity against chloroquine (CQ)sensitive (D6) P. falciparaan (IC50 = 5.3 mu M for the most potent inhibitor) and some were active against E coli (MIC = 6.6 mu g/ml for the most potent inhibitor). (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：879 / 883

页数：5

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