Synthesis and evaluation of potent novel inhibitors of human sulfide:quinone oxidoreductase.

ABSTRACT: Here we report the first small-molecule inhibitors of human sulfide:quinone oxidoreductase (SQOR) that decrease the rate of breakdown of hydrogen sulfide (H₂S), a potent cardioprotective signaling molecule. SQOR is a mitochondrial membrane-bound protein that catalyzes a two-electron oxidation of H₂S to sulfane sulfur (S⁰), using glutathione (or sulfite) and coenzyme Q (CoQ) as S⁰ and electron acceptor, respectively. Inhibition of SQOR may constitute a new approach for the treatment of heart failure with reduced ejection fraction. Starting from top hits identified in a high-throughput screen, we conducted SAR development guided by docking of lead candidates into our crystal structure of SQOR. We identified potent SQOR inhibitors such as 19 which h

SUBMITTER: Baugh SDP 

PROVIDER: S-EPMC8670630 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature