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化学进展 2009, Vol. 21 Issue (09): 1930-1938 前一篇   后一篇

• 综述与评论 •

β-酮脂酰-ACP合成酶（FabH）抑制剂研究进展

刘晓博|李玉艳|尤启冬*   

  1. (中国药科大学药物化学教研室 |南京210009)
  • 收稿日期:2008-09-21 修回日期:2009-01-03 出版日期:2009-09-24 发布日期:2009-09-15
  • 通讯作者: 尤启冬 E-mail:youqidong@gmail.com
  • 基金资助:

    1. 2008年创新药物研究技术平台 2. 创新药物研究孵化基地 3.中国药科大学研究生科研创新基金

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Advances in the Research of β-Ketoacyl-ACP Synthase Ⅲ(FabH) Inhibitors

Liu Xiaobo|Li Yuyan|You Qidong*   

  1. (Department of Medicinal Chemistry, China Pharmacerutical University, Nanjing 210009, China)
  • Received:2008-09-21 Revised:2009-01-03 Online:2009-09-24 Published:2009-09-15
  • Contact: You Qidong E-mail:youqidong@gmail.com

脂肪酸的生物合成对病原细菌的存活至关重要。近年来，在这一生物合成途径中所涉及的关键酶引起了人们的广泛关注。其中β-酮脂酰-ACP合成酶Ⅲ(KAS Ⅲ，FabH)控制着细菌脂肪酸生物合成的起始步骤，普遍存在于病原体中且在人体中无其同源蛋白，成为新型抗菌药物靶标研究的热点。抑制FabH酶活性的小分子抑制剂有望成为对细菌具选择性而对人体无毒的广谱抗菌药。本文对脂肪酸的生物合成，FabH相关结构研究以及目前FabH抑制剂的研究进展进行了综述。

关键词： 脂肪酸合成酶（FAS）, FabH, FabH抑制剂, 结核分枝杆菌

Fatty acid biosynthesis is essential for bacterial survival. In recent years, components of this biosynthetic pathway have aroused wide concern. One fatty acid synthase, FabH (β-Ketoacyl-acyl carrier protein synthase Ⅲ), is a particularly attractive target which catalyzes the initial step of fatty acid biosynthesis. The pivotal role of this essential enzyme combined with its ubiquitous occurrence in bacteria and no homologous protein in human being has made it an attractive new target for the development of new antibacterial agents. Small molecules that inhibit FabH enzymatic activity have the potential to be candidates within a novel class of selective, nontoxic, broad-spectrum antibacterials. In this paper, fatty acid biosynthesis, recent advances in the research of FabH as well as related inhibitors are reviewed.

Contents
1 Introduction
2 Structure of FabH
2.1 FabH
2.2 mtFabH
3 FabH Inhibitors
3.1 Thiolactomycin(TLM)
3.2 Platensimycin and platencin
3.3 Indole compounds
3.4 Benzoylaminobenzoic acid derivatives
3.5 Alkylsulfonyl substituents
3.6 1,2-dithiole-3-ones
3.7 Thiazolidine-2-One 1,1-dioxide
3.8 Alkyl-CoA disulfides
4 Conclusion and perspective

Key words: fatty acid synthase(FAS), FabH, FabH inhibitors, mycobacterium tuberculosis

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