title: Strategies for potentiation of ethionamide and folate antagonists against Mycobacterium tuberculosis.
abstract: Antifolates inhibit de novo folate biosynthesis, whereas ethionamide targets the mycolate synthetic pathway in Mycobacterium tuberculosis. These antibiotics are effective against M. tuberculosis but their use has been hampered by concerns over toxicity and low therapeutic indexes. With the increasing spread of drug-resistant forms, interest in using old drugs for tuberculosis treatment has been renewed. Specific inhibitors targeting resistance mechanisms could sensitize M. tuberculosis to these available, clinically approved drugs. This review discusses recently developed strategies to boost the antituberculous activity of ethionamide and antifolates. These approaches might help broaden the currently limited chemotherapeutic options of not only drug-resistant but also drug-susceptible tuberculosis, which still remains one of the most common infectious diseases in the developing world.
authors.affiliation: Case Western Reserve University School of Medicine, Department of Molecular Biology and Microbiology, Cleveland, OH 44106, USA.
authors.forename: Kerstin A
authors.initials: KA
authors.lastname: Wolff
authors.forename: Liem
authors.initials: L
authors.lastname: Nguyen
mesh_terms: D015195:Drug Design; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods / Q000639:trends; D005000:Ethionamide / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005493:Folic Acid Antagonists / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D005493:Folic Acid Antagonists; D013449:Sulfonamides; D005000:Ethionamide