TBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity

The diarylquinoline F(1)F(O)-ATP synthase inhibitor bedaquiline (BDQ) displays protonophore activity. Thus, uncoupling electron transport from ATP synthesis appears to be a second mechanism of action of this antimycobacterial drug. Here, we show that the new BDQ analogue TBAJ-876 did not retain the...

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Autores principales: Sarathy, Jickky Palmae, Ragunathan, Priya, Cooper, Christopher B., Upton, Anna M., Grüber, Gerhard, Dick, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Mechanisms of Action: Physiological Effects
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985740/
https://www.ncbi.nlm.nih.gov/pubmed/31712198
http://dx.doi.org/10.1128/AAC.01540-19
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author Sarathy, Jickky Palmae
Ragunathan, Priya
Cooper, Christopher B.
Upton, Anna M.
Grüber, Gerhard
Dick, Thomas
author_facet Sarathy, Jickky Palmae
Ragunathan, Priya
Cooper, Christopher B.
Upton, Anna M.
Grüber, Gerhard
Dick, Thomas
author_sort Sarathy, Jickky Palmae
collection PubMed
description The diarylquinoline F(1)F(O)-ATP synthase inhibitor bedaquiline (BDQ) displays protonophore activity. Thus, uncoupling electron transport from ATP synthesis appears to be a second mechanism of action of this antimycobacterial drug. Here, we show that the new BDQ analogue TBAJ-876 did not retain the parental drug’s protonophore activity. Comparative time-kill analyses revealed that both compounds exert the same bactericidal activity. These results suggest that the uncoupler activity is not required for the bactericidal activity of diarylquinolines.
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spelling pubmed-69857402020-02-11 TBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity Sarathy, Jickky Palmae Ragunathan, Priya Cooper, Christopher B. Upton, Anna M. Grüber, Gerhard Dick, Thomas Antimicrob Agents Chemother Mechanisms of Action: Physiological Effects The diarylquinoline F(1)F(O)-ATP synthase inhibitor bedaquiline (BDQ) displays protonophore activity. Thus, uncoupling electron transport from ATP synthesis appears to be a second mechanism of action of this antimycobacterial drug. Here, we show that the new BDQ analogue TBAJ-876 did not retain the parental drug’s protonophore activity. Comparative time-kill analyses revealed that both compounds exert the same bactericidal activity. These results suggest that the uncoupler activity is not required for the bactericidal activity of diarylquinolines. American Society for Microbiology 2020-01-27 /pmc/articles/PMC6985740/ /pubmed/31712198 http://dx.doi.org/10.1128/AAC.01540-19 Text en Copyright © 2020 Sarathy et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Mechanisms of Action: Physiological Effects
Sarathy, Jickky Palmae
Ragunathan, Priya
Cooper, Christopher B.
Upton, Anna M.
Grüber, Gerhard
Dick, Thomas
TBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity
title TBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity
title_full TBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity
title_fullStr TBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity
title_full_unstemmed TBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity
title_short TBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity
title_sort tbaj-876 displays bedaquiline-like mycobactericidal potency without retaining the parental drug’s uncoupler activity
topic Mechanisms of Action: Physiological Effects
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985740/
https://www.ncbi.nlm.nih.gov/pubmed/31712198
http://dx.doi.org/10.1128/AAC.01540-19
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