Title
Selectivity of TMC207 towards mycobacterial ATP synthase compared with that towards the eukaryotic homologue Selectivity of TMC207 towards mycobacterial ATP synthase compared with that towards the eukaryotic homologue
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Washington, D.C. ,
Subject
Biology
Pharmacology. Therapy
Source (journal)
Antimicrobial agents and chemotherapy. - Washington, D.C.
Volume/pages
53(2009) :3 , p. 1290-1292
ISSN
0066-4804
ISI
000263552100070
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
The diarylquinoline TMC207 kills Mycobacterium tuberculosis by specifically inhibiting ATP synthase. We show here that human mitochondrial ATP synthase (50% inhibitory concentration [IC50] of >200 µM) displayed more than 20,000-fold lower sensitivity for TMC207 compared to that of mycobacterial ATP synthase (IC50 of 10 nM). Also, oxygen consumption in mouse liver and bovine heart mitochondria showed very low sensitivity for TMC207. These results suggest that TMC207 may not elicit ATP synthesis-related toxicity in mammalian cells. ATP synthase, although highly conserved between prokaryotes and eukaryotes, may still qualify as an attractive antibiotic target.
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