Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis
Source abstract
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.
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Research context
OpenAlex topics: Tuberculosis Research and Epidemiology · Quinazolinone synthesis and applications · Cancer therapeutics and mechanisms
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Chemistry and Biochemistry, Montana State University, 103 Chemistry and Biochemistry Building, Bozeman, Montana, MT 59717, USA
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
Department of Biological Sciences National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana 500037, India
Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, Indiana, IN 46556, USA
Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921, Singapore
Funding
National Institutes of Health · National Research Foundation Singapore · NRF Investigatorship programme Singapore
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