Syntheses and Structure–Activity Relationships of <i>N</i>-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome <i>bd</i> Oxidase in <i>Mycobacterium tuberculosis</i>
oleh: Sarah M. Hopfner, Bei Shi Lee, Nitin P. Kalia, Marvin J. Miller, Kevin Pethe, Garrett C. Moraski
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2021-09-01 |
Deskripsi
The development of cytochrome <i>bd</i> oxidase (cyt-<i>bd</i>) inhibitors are needed for comprehensive termination of energy production in <i>Mycobacterium tuberculosis</i> (Mtb) to treat tuberculosis infections. Herein, we report on the structure-activity-relationships (SAR) of 22 new <i>N</i>-phenethyl-quinazolin-4-yl-amines that target cyt-<i>bd</i>. Our focused set of compounds was synthesized and screened against three mycobacterial strains: <i>Mycobacterium bovis</i> BCG, <i>Mycobacterium tuberculosis</i> H37Rv and the clinical isolate <i>Mycobacterium tuberculosis</i> N0145 with and without the cytochrome <i>bcc:aa<sub>3</sub></i> inhibitor Q203 in an ATP depletion assay. Two compounds, <b>12a</b> and <b>19a</b>, were more active against all three strains than the naturally derived cyt-<i>bd</i> inhibitor aurachin D.