Preparation and antitubercular activities in vitro and in vivo of novel Schiff bases of isoniazid

Michael J. Hearn, Michael H. Cynamon, Michaeline F. Chen, Rebecca Coppins, Jessica Davis, Helen Joo-On Kang, Abigail Noble, Becky Tu-Sekine, Marianne S. Terrot, Daniella Trombino, Minh Thai, Eleanor R. Webster, Rebecca Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

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 N2-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.

Original languageEnglish (US)
Pages (from-to)4169-4178
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number10
DOIs
StatePublished - Oct 2009

Keywords

  • Acetylation
  • Isoniazid
  • Schiff base
  • Tuberculosis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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