Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs Academic Article uri icon

Overview

MeSH Major

  • Antitubercular Agents
  • Enzyme Inhibitors
  • Mycobacterium tuberculosis
  • Quinone Reductases

abstract

  • Mycobacterium tuberculosis (Mtb) is an obligate aerobe that is capable of long-term persistence under conditions of low oxygen tension. Analysis of the Mtb genome predicts the existence of a branched aerobic respiratory chain terminating in a cytochrome bd system and a cytochrome aa(3) system. Both chains can be initiated with type II NADH:menaquinone oxidoreductase. We present a detailed biochemical characterization of the aerobic respiratory chains from Mtb and show that phenothiazine analogs specifically inhibit NADH:menaquinone oxidoreductase activity. The emergence of drug-resistant strains of Mtb has prompted a search for antimycobacterial agents. Several phenothiazines analogs are highly tuberculocidal in vitro, suppress Mtb growth in a mouse model of acute infection, and represent lead compounds that may give rise to a class of selective antibiotics.

publication date

  • March 22, 2005

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC555520

Digital Object Identifier (DOI)

  • 10.1073/pnas.0500469102

PubMed ID

  • 15767566

Additional Document Info

start page

  • 4548

end page

  • 53

volume

  • 102

number

  • 12