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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Detalles Bibliográficos
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
Descripción
Sumario: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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