2-Aryl-8-aza-3-deazaadenosine analogues of 5′-O-[N-(salicyl)sulfamoyl]adenosine: Nucleoside antibiotics that block siderophore biosynthesis in Mycobacterium tuberculosis

Anna Krajczyk; Joanna Zeidler; Piotr Januszczyk; Surendra Dawadi; Helena I. Boshoff; Clifton E. Barry; Tomasz Ostrowski; Courtney C. Aldrich

doi:10.1016/j.bmc.2016.05.037

2-Aryl-8-aza-3-deazaadenosine analogues of 5′-O-[N-(salicyl)sulfamoyl]adenosine: Nucleoside antibiotics that block siderophore biosynthesis in Mycobacterium tuberculosis

Anna Krajczyk, Joanna Zeidler, Piotr Januszczyk, Surendra Dawadi, Helena I. Boshoff, Clifton E. Barry, Tomasz Ostrowski, Courtney C. Aldrich

Medicinal Chemistry

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

17 Scopus citations

Abstract

A series of 5′-O-[N-(salicyl)sulfamoyl]-2-aryl-8-aza-3-deazaadenosines were designed to block mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) through inhibition of the essential adenylating enzyme MbtA. The synthesis of the 2-aryl-8-aza-3-deazaadenosine nucleosides featured sequential copper-free palladium-catalyzed Sonogashira coupling of a precursor 4-cyano-5-iodo-1,2,3-triazolonucleoside with terminal alkynes and a Minakawa-Matsuda annulation reaction. These modified nucleosides were shown to inhibit MbtA with apparent K_ivalues ranging from 6.1 to 25 nM and to inhibit Mtb growth under iron-deficient conditions with minimum inhibitory concentrations ranging from 12.5 to >50 μM.

Original language	English (US)
Pages (from-to)	3133-3143
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	24
Issue number	14
DOIs	https://doi.org/10.1016/j.bmc.2016.05.037
State	Published - 2016

Bibliographical note

Funding Information:
This work was supported by the Polish Ministry of Science and Higher Education grant no. N N405 2516 33 (J.Z.), under statutory financing, and under the KNOW program. It was also supported by a grant from the NIH ( AI070219 to C.C.A.) and the Intramural Research Program of the NIAID , NIH (C.E.B.). We wish to thank Dr. Lukasz Marczak and Dr. Barbara Swarcewicz for MS spectra measurements.

Publisher Copyright:
© 2016 Elsevier Ltd. All rights reserved.

Keywords

8-Aza-3-deazaadenosine
Adenylation inhibitor
Modified nucleoside
Siderophore biosynthesis
Tuberculosis

UN SDGs

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

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10.1016/j.bmc.2016.05.037

http://europepmc.org/articles/pmc4914392

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Krajczyk, A., Zeidler, J., Januszczyk, P., Dawadi, S., Boshoff, H. I., Barry, C. E., Ostrowski, T., & Aldrich, C. C. (2016). 2-Aryl-8-aza-3-deazaadenosine analogues of 5′-O-[N-(salicyl)sulfamoyl]adenosine: Nucleoside antibiotics that block siderophore biosynthesis in Mycobacterium tuberculosis. Bioorganic and Medicinal Chemistry, 24(14), 3133-3143. https://doi.org/10.1016/j.bmc.2016.05.037

2-Aryl-8-aza-3-deazaadenosine analogues of 5′-O-[N-(salicyl)sulfamoyl]adenosine: Nucleoside antibiotics that block siderophore biosynthesis in Mycobacterium tuberculosis. / Krajczyk, Anna; Zeidler, Joanna; Januszczyk, Piotr et al.
In: Bioorganic and Medicinal Chemistry, Vol. 24, No. 14, 2016, p. 3133-3143.

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

Krajczyk, A, Zeidler, J, Januszczyk, P, Dawadi, S, Boshoff, HI, Barry, CE, Ostrowski, T & Aldrich, CC 2016, '2-Aryl-8-aza-3-deazaadenosine analogues of 5′-O-[N-(salicyl)sulfamoyl]adenosine: Nucleoside antibiotics that block siderophore biosynthesis in Mycobacterium tuberculosis', Bioorganic and Medicinal Chemistry, vol. 24, no. 14, pp. 3133-3143. https://doi.org/10.1016/j.bmc.2016.05.037

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abstract = "A series of 5′-O-[N-(salicyl)sulfamoyl]-2-aryl-8-aza-3-deazaadenosines were designed to block mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) through inhibition of the essential adenylating enzyme MbtA. The synthesis of the 2-aryl-8-aza-3-deazaadenosine nucleosides featured sequential copper-free palladium-catalyzed Sonogashira coupling of a precursor 4-cyano-5-iodo-1,2,3-triazolonucleoside with terminal alkynes and a Minakawa-Matsuda annulation reaction. These modified nucleosides were shown to inhibit MbtA with apparent Kivalues ranging from 6.1 to 25 nM and to inhibit Mtb growth under iron-deficient conditions with minimum inhibitory concentrations ranging from 12.5 to >50 μM.",

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2-Aryl-8-aza-3-deazaadenosine analogues of 5′-O-[N-(salicyl)sulfamoyl]adenosine: Nucleoside antibiotics that block siderophore biosynthesis in Mycobacterium tuberculosis

Abstract

Bibliographical note

Keywords

UN SDGs

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