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Current Status of Target-Based Antimycobacterial Natural Products

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The situation of tuberculosis disease has recently been complicated by the human immunodeficiency virus epidemic and the increased prevalence of multi-drug resistant strains of Mycobacterium tuberculosis. The new drugs which are affordable and more effective compared to clinically used, are required to target resistant strains of M. tuberculosis and emerging pathogens, such as M. avium complex. Most of the reported natural products exhibited antimycobacterial activity against whole mycobacteria species viz. M. tuberculosis, M. avium complex and M. bovis. An analysis of the literature examples of target-based natural products reveals insights into mechanism of their antimycobacterial activity that might help medicinal chemists to design and develop novel antimycobacterial compounds. In the present review the attempt has been made to cover target-based natural products that exhibited antimycobacterial activity. The enzymes involved in the metabolism of mycolic acids represent attractive targets for the design of new anti-mycobacterial agents, as mycolic acids are vital in bacterial survival. The antimycobacterial targets such as β-ketoacyl-acyl-carrier protein synthases, KasA and KasB (belong to the fatty-acid synthase type II system involved in fatty acid and mycolic acid biosynthesis), inhA, an enoyl-acyl carrier protein (ACP) reductase, mycothiol-S-conjugate Amidase (MCA) and inhibitors (of natural product origin) acting on these are discussed in detail.

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Keywords: KasB; Mycobacterium tuberculosis; an enoyl-acyl carrier protein reductase (inhA); mtFabH; mycolic acids; mycothiol-S-conjugate amidase; natural products; β-ketoacyl-acyl-carrier protein synthases KasA

Document Type: Research Article

Affiliations: Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, SAS Nagar, 160 062, Punjab, India.

Publication date: April 1, 2006

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  • Anti-Infective Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new anti-infective agents.
    Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in anti-infective medicinal chemistry.

    Anti-Infective Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in anti-infective drug discovery.
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