Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 44, Issue 10, Pages 4169-4178Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2009.05.009
Keywords
Tuberculosis; Acetylation; Isoniazid; Schiff base
Categories
Funding
- US National Institutes of Health (NIH) [1 R15 A148397-01]
- Wellesley College
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Structural modification of the frontline antitubercular isonicotinic acid hydrazide (INH) provides lipophilic adaptations (3-46) of the drug in which the hydrazine moiety of the parent compound has been chemically blocked from the deactivating process of N-2-acetylation by N-arylaminoacetyl transferases. As a class, these compounds show high levels of activity against Mycobacterium tuberculosis in vitro and in tuberculosis-infected macrophages. They provide strong protection in tuberculosis-infected mice and have low toxicity. With some representatives of this class achieving early peak plasma concentrations approximately three orders of magnitude above minimum inhibitory concentration, they may serve as tools for improving our understanding of INH-based treatment modalities, particularly for those patients chronically underdosed in conventional INH therapy. (C) 2009 Elsevier Masson SAS. All rights reserved.
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