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Syntheses and Structure-Activity Relationships of N -Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis .

Sarah M HopfnerBei Shi LeeNitin Pal KaliaMarvin J MillerKevin PetheGarrett C Moraski
Published in: Applied sciences (Basel, Switzerland) (2021)
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:aa 3 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.
Keyphrases
  • mycobacterium tuberculosis
  • pulmonary tuberculosis
  • escherichia coli
  • high throughput
  • hepatitis c virus
  • single cell
  • hiv infected