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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Bibliographic Details
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
Description
Summary: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.

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