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Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones

8-Nitro-1,3-benzothiazin-4-ones (BTZs), with BTZ043 and PBTZ169 as the most advanced compounds, represent a new class of potent antitubercular agents, which irreversibly inhibit decaprenylphosphoryl-β-d-ribose-2′-epimerase (DprE1), an enzyme crucial for cell wall synthesis in the pathogen Mycobacter...

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Autores principales: Madikizela, Balungile, Eckhardt, Tamira, Goddard, Richard, Richter, Adrian, Lins, Anika, Lehmann, Christoph, Imming, Peter, Seidel, Rüdiger W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192043/
https://www.ncbi.nlm.nih.gov/pubmed/34131377
http://dx.doi.org/10.1007/s00044-021-02735-4
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author Madikizela, Balungile
Eckhardt, Tamira
Goddard, Richard
Richter, Adrian
Lins, Anika
Lehmann, Christoph
Imming, Peter
Seidel, Rüdiger W.
author_facet Madikizela, Balungile
Eckhardt, Tamira
Goddard, Richard
Richter, Adrian
Lins, Anika
Lehmann, Christoph
Imming, Peter
Seidel, Rüdiger W.
author_sort Madikizela, Balungile
collection PubMed
description 8-Nitro-1,3-benzothiazin-4-ones (BTZs), with BTZ043 and PBTZ169 as the most advanced compounds, represent a new class of potent antitubercular agents, which irreversibly inhibit decaprenylphosphoryl-β-d-ribose-2′-epimerase (DprE1), an enzyme crucial for cell wall synthesis in the pathogen Mycobacterium tuberculosis. Synthesis, structural characterization and in vitro testing against Mycobacterium aurum DSM 43999 and M. tuberculosis H(37)Rv of halogenated 2-(4-ethoxycarbonylpiperazin-1-yl)-1,3-benzothiazin-4-ones lacking a nitro group are reported. X-ray crystallography reveals that the structure of the BTZ scaffold can significantly deviate from planarity. In contrast to recent reports, the results of the present study indicate that further investigation of halogenated non-nitro BTZs for antitubercular activity is less than a promising approach.
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spelling pubmed-81920432021-06-11 Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones Madikizela, Balungile Eckhardt, Tamira Goddard, Richard Richter, Adrian Lins, Anika Lehmann, Christoph Imming, Peter Seidel, Rüdiger W. Med Chem Res Original Research 8-Nitro-1,3-benzothiazin-4-ones (BTZs), with BTZ043 and PBTZ169 as the most advanced compounds, represent a new class of potent antitubercular agents, which irreversibly inhibit decaprenylphosphoryl-β-d-ribose-2′-epimerase (DprE1), an enzyme crucial for cell wall synthesis in the pathogen Mycobacterium tuberculosis. Synthesis, structural characterization and in vitro testing against Mycobacterium aurum DSM 43999 and M. tuberculosis H(37)Rv of halogenated 2-(4-ethoxycarbonylpiperazin-1-yl)-1,3-benzothiazin-4-ones lacking a nitro group are reported. X-ray crystallography reveals that the structure of the BTZ scaffold can significantly deviate from planarity. In contrast to recent reports, the results of the present study indicate that further investigation of halogenated non-nitro BTZs for antitubercular activity is less than a promising approach. Springer US 2021-06-10 2021 /pmc/articles/PMC8192043/ /pubmed/34131377 http://dx.doi.org/10.1007/s00044-021-02735-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Research
Madikizela, Balungile
Eckhardt, Tamira
Goddard, Richard
Richter, Adrian
Lins, Anika
Lehmann, Christoph
Imming, Peter
Seidel, Rüdiger W.
Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones
title Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones
title_full Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones
title_fullStr Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones
title_full_unstemmed Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones
title_short Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones
title_sort synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192043/
https://www.ncbi.nlm.nih.gov/pubmed/34131377
http://dx.doi.org/10.1007/s00044-021-02735-4
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