A new version of this entry is available:
Loading...
Article
2023
Exploring ND-011992, a quinazoline-type inhibitor targeting quinone reductases and quinol oxidases
Exploring ND-011992, a quinazoline-type inhibitor targeting quinone reductases and quinol oxidases
Abstract (English)
Bacterial energy metabolism has become a promising target for next-generation tuberculosis chemotherapy. One strategy to hamper ATP production is to inhibit the respiratory oxidases. The respiratory chain of Mycobacterium tuberculosis comprises a cytochrome bcc:aa3 and a cytochrome bd ubiquinol oxidase that require a combined approach to block their activity. A quinazoline-type compound called ND-011992 has previously been reported to ineffectively inhibit bd oxidases, but to act bactericidal in combination with inhibitors of cytochrome bcc:aa3 oxidase. Due to the structural similarity of ND-011992 to quinazoline-type inhibitors of respiratory complex I, we suspected that this compound is also capable of blocking other respiratory chain complexes. Here, we synthesized ND-011992 and a bromine derivative to study their effect on the respiratory chain complexes of Escherichia coli. And indeed, ND-011992 was found to inhibit respiratory complex I and bo3 oxidase in addition to bd-I and bd-II oxidases. The IC50 values are all in the low micromolar range, with inhibition of complex I providing the lowest value with an IC50 of 0.12 µM. Thus, ND-011992 acts on both, quinone reductases and quinol oxidases and could be very well suited to regulate the activity of the entire respiratory chain.
File is subject to an embargo until
This is a correction to:
A correction to this entry is available:
This is a new version of:
Notes
Publication license
Publication series
Published in
Scientific reports, 13 (2023), 12226.
https://doi.org/10.1038/s41598-023-39430-w.
ISSN: 2045-2322
Other version
Faculty
Institute
Examination date
Supervisor
Edition / version
Citation
DOI
ISSN
ISBN
Language
English
Publisher
Publisher place
Classification (DDC)
610 Medicine and health
Collections
Original object
Free keywords
Standardized keywords (GND)
Sustainable Development Goals
BibTeX
@article{Kägi2023,
doi = {10.1038/s41598-023-39430-w},
author = {Kägi, Jan and Sloan, Willough and Schimpf, Johannes et al.},
title = {Exploring ND-011992, a quinazoline-type inhibitor targeting quinone reductases and quinol oxidases},
journal = {Scientific reports},
year = {202},
volume = {13},
}