TBAJ-876 displays bedaquiline-like mycobactericidal potency without retaining the parental drug’s uncoupler activity

TBAJ-876 displays bedaquiline-like mycobactericidal potency without retaining the parental drug’s uncoupler activity

The diarylquinoline F1FO-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 pare...

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Main Authors: Sarathy, Jickky Palmae, Ragunathan, Priya, Cooper, Christopher B., Upton, Anna M., Grüber, Gerhard, Dick, Thomas
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2020
Subjects:
Science::Biological sciences::Biochemistry
Science::Biological sciences::Molecular biology
TBAJ-876
Bedaquiline
Online Access:https://hdl.handle.net/10356/138548
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1385482023-02-28T16:57:49Z 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 School of Biological Sciences Science::Biological sciences::Biochemistry Science::Biological sciences::Molecular biology TBAJ-876 Bedaquiline The diarylquinoline F1FO-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. NRF (Natl Research Foundation, S’pore) NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) Published version 2020-05-08T02:22:12Z 2020-05-08T02:22:12Z 2020 Journal Article Sarathy, J. P., Ragunathan, P., Cooper, C. B., Upton, A. M., Grüber, G., & Dick, T. (2020). TBAJ-876 displays bedaquiline-like mycobactericidal potency without retaining the parental drug’s uncoupler activity. Antimicrobial Agents and Chemotherapy, 64(2), e01540-19-. doi:10.1128/AAC.01540-19 0066-4804 https://hdl.handle.net/10356/138548 10.1128/AAC.01540-19 31712198 2-s2.0-85078571665 2 64 en Antimicrobial Agents and Chemotherapy © 2020 Sarathy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences::Biochemistry
Science::Biological sciences::Molecular biology
TBAJ-876
Bedaquiline
spellingShingle Science::Biological sciences::Biochemistry
Science::Biological sciences::Molecular biology
TBAJ-876
Bedaquiline
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
description The diarylquinoline F1FO-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.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Sarathy, Jickky Palmae
Ragunathan, Priya
Cooper, Christopher B.
Upton, Anna M.
Grüber, Gerhard
Dick, Thomas
format Article
author Sarathy, Jickky Palmae
Ragunathan, Priya
Cooper, Christopher B.
Upton, Anna M.
Grüber, Gerhard
Dick, Thomas
author_sort Sarathy, Jickky Palmae
title 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_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_sort tbaj-876 displays bedaquiline-like mycobactericidal potency without retaining the parental drug’s uncoupler activity
publishDate 2020
url https://hdl.handle.net/10356/138548
_version_ 1759855798720135168

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