Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis

The development of cytochrome bd oxidase (cyt-bd) inhibitors are needed for comprehensive termination of energy production in Mycobacterium tuberculosis (Mtb) to treat tuberculosis infections. Herein, we report on the structure-activity-relationships (SAR) of 22 new N-phenethyl-quinazolin-4-yl-amine...

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Autores principales: Hopfner, Sarah M., Lee, Bei Shi, Kalia, Nitin P., Miller, Marvin J., Pethe, Kevin, Moraski, Garrett C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873234/
https://www.ncbi.nlm.nih.gov/pubmed/36698770
http://dx.doi.org/10.3390/app11199092
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author Hopfner, Sarah M.
Lee, Bei Shi
Kalia, Nitin P.
Miller, Marvin J.
Pethe, Kevin
Moraski, Garrett C.
author_facet Hopfner, Sarah M.
Lee, Bei Shi
Kalia, Nitin P.
Miller, Marvin J.
Pethe, Kevin
Moraski, Garrett C.
author_sort Hopfner, Sarah M.
collection PubMed
description The development of cytochrome bd oxidase (cyt-bd) inhibitors are needed for comprehensive termination of energy production in Mycobacterium tuberculosis (Mtb) to treat tuberculosis infections. Herein, we report on the structure-activity-relationships (SAR) of 22 new N-phenethyl-quinazolin-4-yl-amines that target cyt-bd. Our focused set of compounds was synthesized and screened against three mycobacterial strains: Mycobacterium bovis BCG, Mycobacterium tuberculosis H37Rv and the clinical isolate Mycobacterium tuberculosis N0145 with and without the cytochrome bcc:aa(3) inhibitor Q203 in an ATP depletion assay. Two compounds, 12a and 19a, were more active against all three strains than the naturally derived cyt-bd inhibitor aurachin D.
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spelling pubmed-98732342023-01-24 Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis Hopfner, Sarah M. Lee, Bei Shi Kalia, Nitin P. Miller, Marvin J. Pethe, Kevin Moraski, Garrett C. Appl Sci (Basel) Article The development of cytochrome bd oxidase (cyt-bd) inhibitors are needed for comprehensive termination of energy production in Mycobacterium tuberculosis (Mtb) to treat tuberculosis infections. Herein, we report on the structure-activity-relationships (SAR) of 22 new N-phenethyl-quinazolin-4-yl-amines that target cyt-bd. Our focused set of compounds was synthesized and screened against three mycobacterial strains: Mycobacterium bovis BCG, Mycobacterium tuberculosis H37Rv and the clinical isolate Mycobacterium tuberculosis N0145 with and without the cytochrome bcc:aa(3) inhibitor Q203 in an ATP depletion assay. Two compounds, 12a and 19a, were more active against all three strains than the naturally derived cyt-bd inhibitor aurachin D. 2021-10 2021-09-29 /pmc/articles/PMC9873234/ /pubmed/36698770 http://dx.doi.org/10.3390/app11199092 Text en https://creativecommons.org/licenses/by/4.0/This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hopfner, Sarah M.
Lee, Bei Shi
Kalia, Nitin P.
Miller, Marvin J.
Pethe, Kevin
Moraski, Garrett C.
Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis
title Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis
title_full Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis
title_fullStr Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis
title_full_unstemmed Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis
title_short Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis
title_sort syntheses and structure–activity relationships of n-phenethyl-quinazolin-4-yl-amines as potent inhibitors of cytochrome bd oxidase in mycobacterium tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873234/
https://www.ncbi.nlm.nih.gov/pubmed/36698770
http://dx.doi.org/10.3390/app11199092
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