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Article

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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Department of Chemistry and Biochemistry, Montana State University, 103 Chemistry and Biochemistry Building, Bozeman, Montana, MT 59717, USA
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School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
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Department of Biological Sciences National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana 500037, India
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Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, Indiana, IN 46556, USA
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Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921, Singapore
*
Author to whom correspondence should be addressed.
Academic Editor: Alfonso Zambon
Appl. Sci. 2021, 11(19), 9092; https://doi.org/10.3390/app11199092
Received: 10 August 2021 / Revised: 14 September 2021 / Accepted: 22 September 2021 / Published: 29 September 2021
(This article belongs to the Special Issue Antitubercular Drugs: Synthesis, Mechanism and Application)
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. View Full-Text
Keywords: tuberculosis; drug development; structure–activity relationships; quinazoline; energy metabolism; cytochrome bd oxidase tuberculosis; drug development; structure–activity relationships; quinazoline; energy metabolism; cytochrome bd oxidase
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MDPI and ACS Style

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

AMA Style

Hopfner SM, Lee BS, Kalia NP, Miller MJ, Pethe K, Moraski GC. Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis. Applied Sciences. 2021; 11(19):9092. https://doi.org/10.3390/app11199092

Chicago/Turabian Style

Hopfner, Sarah M., Bei S. Lee, Nitin P. Kalia, Marvin J. Miller, Kevin Pethe, and Garrett C. Moraski. 2021. "Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis" Applied Sciences 11, no. 19: 9092. https://doi.org/10.3390/app11199092

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