Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis
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Date
2021-09
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
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.
Description
Keywords
tuberculosis, drug development, structure-activity, relationships, quinazoline, energy metabolism, cytochrome bd oxidase
Citation
Hopfner, S.M.; Lee, B.S.; Kalia, N.P.; Miller, M.J.; Pethe, K.; Moraski, G.C. Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis. Appl. Sci. 2021, 11, 9092. https:// doi.org/10.3390/app11199092