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

19 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

UN SDGs

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

SDG 3 Good Health and Well-being

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

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

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.

KW - Enoyl-ACP reductase (InhA)

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

UN SDGs

Keywords

ASJC Scopus subject areas

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