title: Preparation and antitubercular activities in vitro and in vivo of novel Schiff bases of isoniazid.
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 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.
authors.affiliation: Department of Chemistry, Wellesley College, 106 Central Street, Wellesley, MA 02481, USA. mhearn@wellesley.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hearn
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cynamon
authors.forename: Michaeline F
authors.initials: MF
authors.lastname: Chen
authors.forename: Rebecca
authors.initials: R
authors.lastname: Coppins
authors.forename: Jessica
authors.initials: J
authors.lastname: Davis
authors.forename: Helen
authors.initials: H
authors.lastname: Joo-On Kang
authors.forename: Abigail
authors.initials: A
authors.lastname: Noble
authors.forename: Becky
authors.initials: B
authors.lastname: Tu-Sekine
authors.forename: Marianne S
authors.initials: MS
authors.lastname: Terrot
authors.forename: Daniella
authors.initials: D
authors.lastname: Trombino
authors.forename: Minh
authors.initials: M
authors.lastname: Thai
authors.forename: Eleanor R
authors.initials: ER
authors.lastname: Webster
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D007538:Isoniazid / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012545:Schiff Bases / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D012545:Schiff Bases; D007538:Isoniazid