Structure guided generation of thieno[3,2-d]pyrimidin-4-amine Mycobacterium tuberculosis bd oxidase inhibitors.

ABSTRACT: Cytochrome bd oxidase (Cyt-bd) is an attractive drug target in Mycobacterium tuberculosis, especially in the context of developing a drug combination targeting energy metabolism. However, currently few synthetically assessable scaffolds target Cyt-bd. Herein, we report that thieno[3,2-d]pyrimidin-4-amines inhibit Cyt-bd, and report an initial structure-activity-relationship (SAR) of 13 compounds in three mycobacterial strains: Mycobacterium bovis BCG, Mycobacterium tuberculosis H37Rv and Mycobacterium tuberculosis clinical isolate N0145 in an established ATP depletion assay with or without the cytochrome bcc : aa ₃ (QcrB) inhibitor Q203. All compounds displayed activity against M. bovis BCG and t

SUBMITTER: Hopfner SM 

PROVIDER: S-EPMC8130631 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature