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Molecules 2012, 17(5), 4770-4781; doi:10.3390/molecules17054770

Synthesis of Potent Inhibitors of β-Ketoacyl-Acyl Carrier Protein Synthase III as Potential Antimicrobial Agents

1
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China
2
Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
*
Author to whom correspondence should be addressed.
Received: 26 December 2011 / Revised: 11 April 2012 / Accepted: 16 April 2012 / Published: 25 April 2012
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Mycobacterium tuberculosis FabH, an essential enzyme in the mycolic acid biosynthetic pathway, is an attractive target for novel anti-tubercolosis agents. Structure-based design and synthesis of 1-(4-carboxybutyl)-4-(4-(substituted benzyloxy)phenyl)-1H-pyrrole-2-carboxylic acid derivatives 7a–h, a subset of eight potential FabH inhibitors, is described in this paper. The Vilsmeier-Haack reaction was employed as a key step. The structures of all the newly synthesized compounds were identified by IR, 1H-NMR, 13C-NMR, ESI-MS and HRMS. The alamarBlue™ microassay was employed to evaluate the compounds 7a–h against Mycobacterium tuberculosis H37Rv. The results demonstrate that the compound 7d possesses good in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Minimum Inhibitory Concentration value [MIC], 12.5 µg/mL).These compounds may prove useful in the discovery and development of new anti-tuberculosis drugs.
Keywords: tuberculosis; Mycobacterium tuberculosis FabH; structure based design; synthesis; alamarBlue™ microassay tuberculosis; Mycobacterium tuberculosis FabH; structure based design; synthesis; alamarBlue™ microassay
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Liu, Y.; Zhong, W.; Li, R.-J.; Li, S. Synthesis of Potent Inhibitors of β-Ketoacyl-Acyl Carrier Protein Synthase III as Potential Antimicrobial Agents. Molecules 2012, 17, 4770-4781.

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