Open AccessTBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity
Author(s) -
Jickky Palmae Sarathy,
Priya Ragunathan,
Christopher B. Cooper,
Anna M. Upton,
Gerhard Grüber,
Thomas Dick
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01540-19
Subject(s) - protonophore , bedaquiline , atp synthase , potency , drug , pharmacology , mechanism of action , chemistry , biochemistry , biology , medicine , mitochondrion , in vitro , enzyme , tuberculosis , mycobacterium tuberculosis , pathology
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.