Discovery of 8-Hydroxyquinoline as a Histamine Receptor 2 Blocker Scaffold.

ABSTRACT: Histamine receptor 2 (HR_H2) activation in the stomach results in gastric acid secretion, and HR_H2 blockers are used for the treatment of peptidic ulcers and acid reflux. Over-the-counter HR_H2 blockers carry a five-membered aromatic heterocycle, with two of them additionally carrying a tertiary amine that decomposes to N-nitrosodimethylamine, a human carcinogen. To discover a novel HR_H2 blocker scaffold to serve in the development of next-generation HR_H2 blockers, we developed an HR_H2-based sensor in yeast by linking human HR_H2 activation to cell luminescence. We used the HR_H2-based sensor to screen a 403-member anti-infection chemical library and identified three HR_H2 blockers, chlorquinaldol

SUBMITTER: Marquez-Gomez PL 

PROVIDER: S-EPMC9396701 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature