Discovery of Potent Benzothiazole Inhibitors of Oxidoreductase NQO2, a Target for Inflammation and Cancer.

ABSTRACT: Inhibitors of NQO2 (NRH: quinone oxidoreductase) have potential application in several areas of medicine and pharmacology, including cancer, neurodegeneration (PD and AD), stroke, and diabetes. Here, resveratrol, a known inhibitor of NQO2, was used as the lead by replacing the double bond in resveratrol with a benzothiazole scaffold. Fifty-five benzothiazoles were designed as NQO2 inhibitors and synthesized, comprising five benzothiazole series with 3,5-dimethoxy, 2,4-dimethoxy, 2,5-dimethoxy, 3,4-dimethoxy, and 3,4,5-trimethoxy substituents, the key synthetic step being a Jacobson cyclisation with the appropriate thiobenzamide. All compounds were evaluated in an NQO2 enzyme inhibition assay, with four compounds having IC₅₀ values of <100 nM. The most active (IC₅₀ 25

SUBMITTER: Belgath AA 

PROVIDER: S-EPMC11593696 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature