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

doi:10.1016/j.ejmech.2009.05.009

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 journal › Article › peer-review

120 Scopus citations

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 language	English (US)
Pages (from-to)	4169-4178
Number of pages	10
Journal	European Journal of Medicinal Chemistry
Volume	44
Issue number	10
DOIs	https://doi.org/10.1016/j.ejmech.2009.05.009
State	Published - Oct 2009
Externally published	Yes

Keywords

Acetylation
Isoniazid
Schiff base
Tuberculosis

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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10.1016/j.ejmech.2009.05.009

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Hearn, M. J., Cynamon, M. H., Chen, M. F., Coppins, R., Davis, J., Joo-On Kang, H., Noble, A., Tu-Sekine, B., Terrot, M. S., Trombino, D., Thai, M., Webster, E. R., & Wilson, R. (2009). Preparation and antitubercular activities in vitro and in vivo of novel Schiff bases of isoniazid. European Journal of Medicinal Chemistry, 44(10), 4169-4178. https://doi.org/10.1016/j.ejmech.2009.05.009

Hearn, MJ, Cynamon, MH, Chen, MF, Coppins, R, Davis, J, Joo-On Kang, H, Noble, A, Tu-Sekine, B, Terrot, MS, Trombino, D, Thai, M, Webster, ER & Wilson, R 2009, 'Preparation and antitubercular activities in vitro and in vivo of novel Schiff bases of isoniazid', European Journal of Medicinal Chemistry, vol. 44, no. 10, pp. 4169-4178. https://doi.org/10.1016/j.ejmech.2009.05.009

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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 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.",

keywords = "Acetylation, Isoniazid, Schiff base, Tuberculosis",

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

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doi = "10.1016/j.ejmech.2009.05.009",

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AU - Chen, Michaeline F.

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AU - Davis, Jessica

AU - Joo-On Kang, Helen

AU - Noble, Abigail

AU - Tu-Sekine, Becky

AU - Terrot, Marianne S.

AU - Trombino, Daniella

AU - Thai, Minh

AU - Webster, Eleanor R.

AU - Wilson, Rebecca

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KW - Acetylation

KW - Isoniazid

KW - Schiff base

KW - Tuberculosis

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

Abstract

Keywords

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