Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis

Laurent Bonnac; Guang Yao Gao; Liqiang Chen; Krzysztof Felczak; Eric M. Bennett; Hua Xu; Tae Soo Kim; Nina Liu; Hye Won Oh; Peter J. Tonge; Krzysztof W. Pankiewicz

doi:10.1016/j.bmcl.2007.05.084

Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis

Laurent Bonnac, Guang Yao Gao, Liqiang Chen, Krzysztof Felczak, Eric M. Bennett, Hua Xu, Tae Soo Kim, Nina Liu, Hye Won Oh, Peter J. Tonge, Krzysztof W. Pankiewicz

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

The chemical synthesis of 4-phenoxybenzamide adenine dinucleotide (3), a NAD analogue which mimics isoniazid-NAD adduct and inhibits Mycobacterium tuberculosis NAD-dependent enoyl-ACP reductase (InhA), is reported. The 4-phenoxy benzamide riboside (1) has been prepared as a key intermediate, converted into its 5′-mononucleotide (2), and coupled with AMP imidazolide to give the desired NAD analogue 3. It inhibits InhA with IC₅₀ = 27 μM.

Original language	English (US)
Pages (from-to)	4588-4591
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2007.05.084
State	Published - Aug 15 2007
Externally published	Yes

Keywords

Enoyl-ACP reductase (InhA)
Fragment-based drug discovery
Isoniazid
M. tuberculosis
NAD analogues

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2007.05.084

Cite this

Bonnac, L., Gao, G. Y., Chen, L., Felczak, K., Bennett, E. M., Xu, H., Kim, T. S., Liu, N., Oh, H. W., Tonge, P. J., & Pankiewicz, K. W. (2007). Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis. Bioorganic and Medicinal Chemistry Letters, 17(16), 4588-4591. https://doi.org/10.1016/j.bmcl.2007.05.084

Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis. / Bonnac, Laurent; Gao, Guang Yao; Chen, Liqiang et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 16, 15.08.2007, p. 4588-4591.

Research output: Contribution to journal › Article › peer-review

Bonnac, L, Gao, GY, Chen, L, Felczak, K, Bennett, EM, Xu, H, Kim, TS, Liu, N, Oh, HW, Tonge, PJ & Pankiewicz, KW 2007, 'Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 16, pp. 4588-4591. https://doi.org/10.1016/j.bmcl.2007.05.084

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abstract = "The chemical synthesis of 4-phenoxybenzamide adenine dinucleotide (3), a NAD analogue which mimics isoniazid-NAD adduct and inhibits Mycobacterium tuberculosis NAD-dependent enoyl-ACP reductase (InhA), is reported. The 4-phenoxy benzamide riboside (1) has been prepared as a key intermediate, converted into its 5′-mononucleotide (2), and coupled with AMP imidazolide to give the desired NAD analogue 3. It inhibits InhA with IC50 = 27 μM.",

keywords = "Enoyl-ACP reductase (InhA), Fragment-based drug discovery, Isoniazid, M. tuberculosis, NAD analogues",

author = "Laurent Bonnac and Gao, {Guang Yao} and Liqiang Chen and Krzysztof Felczak and Bennett, {Eric M.} and Hua Xu and Kim, {Tae Soo} and Nina Liu and Oh, {Hye Won} and Tonge, {Peter J.} and Pankiewicz, {Krzysztof W.}",

note = "Funding Information: These studies were funded by the Center for Drug Design, University of Minnesota. We thank the Minnesota Supercomputing Institute for computer time. ",

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doi = "10.1016/j.bmcl.2007.05.084",

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AU - Bonnac, Laurent

AU - Gao, Guang Yao

AU - Chen, Liqiang

AU - Felczak, Krzysztof

AU - Bennett, Eric M.

AU - Xu, Hua

AU - Kim, Tae Soo

AU - Liu, Nina

AU - Oh, Hye Won

AU - Tonge, Peter J.

AU - Pankiewicz, Krzysztof W.

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AB - The chemical synthesis of 4-phenoxybenzamide adenine dinucleotide (3), a NAD analogue which mimics isoniazid-NAD adduct and inhibits Mycobacterium tuberculosis NAD-dependent enoyl-ACP reductase (InhA), is reported. The 4-phenoxy benzamide riboside (1) has been prepared as a key intermediate, converted into its 5′-mononucleotide (2), and coupled with AMP imidazolide to give the desired NAD analogue 3. It inhibits InhA with IC50 = 27 μM.

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KW - Fragment-based drug discovery

KW - Isoniazid

KW - M. tuberculosis

KW - NAD analogues

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Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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