Syntheses and structure–activity relationships of N-phenethyl-quinazolin-4-yl-amines as potent inhibitors of cytochrome bd oxidase in Mycobacterium tuberculosis

Syntheses and structure–activity relationships of N-phenethyl-quinazolin-4-yl-amines as potent inhibitors of cytochrome bd oxidase in Mycobacterium tuberculosis

The development of cytochrome bd oxidase (cyt‐bd) inhibitors are needed for comprehensive termination of energy production in Mycobacterium tuberculosis (Mtb) to treat tuberculosis infections. Herein, we report on the structure‐activity‐relationships (SAR) of 22 new N‐phenethyl‐quinazolin‐4‐ yl‐amin...

Full description

Saved in:
Bibliographic Details
Main Authors: Hopfner, Sarah M., Lee, Bei Shi, Kalia, Nitin P., Miller Marvin J., Pethe, Kevin, Moraski, Garrett C.
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2022
Subjects:
Science::Biological sciences
Tuberculosis
Drug Development
Online Access:https://hdl.handle.net/10356/153933
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
Description
Summary:The development of cytochrome bd oxidase (cyt‐bd) inhibitors are needed for comprehensive termination of energy production in Mycobacterium tuberculosis (Mtb) to treat tuberculosis infections. Herein, we report on the structure‐activity‐relationships (SAR) of 22 new N‐phenethyl‐quinazolin‐4‐ yl‐amines that target cyt‐bd. Our focused set of compounds was synthesized and screened against three mycobacterial strains: Mycobacterium bovis BCG, Mycobacterium tuberculosis H37Rv and the clinical isolate Mycobacterium tuberculosis N0145 with and without the cytochrome bcc:aa3 inhibitor Q203 in an ATP depletion assay. Two compounds, 12a and 19a, were more active against all three strains than the naturally derived cyt‐bd inhibitor aurachin D.

Similar Items