RESUMEN
Benzisothiazole dioxide compound was reported to agonize HIF-2 stabilization and improve EPO production, thus conceiving a potential strategy to treat disease with chronic hypoxia exemplified by renal anemia. Herein, on the bases of multiple molecular and cellular assays, a series of benzisothiazole derivatives have been synthesized and their structure-activity relationship was evaluated. The SAR and molecular docking studies have revealed the structural insights on the rational design of HIF-2 agonist and discovered a more potential 5-bromine substituted analogue, which showed 2-4 times improvement of HIF-2 downstream gene transcriptions, including EPO production. The present results suggest the therapeutic potential of the compounds for diseases related to EPO insufficiency.
Asunto(s)
Anemia , Eritropoyetina , Humanos , Eritropoyetina/farmacología , Eritropoyetina/genética , Simulación del Acoplamiento Molecular , Anemia/tratamiento farmacológico , Factores de Transcripción con Motivo Hélice-Asa-Hélice BásicoRESUMEN
Two new flavonoids, cryunchalcone (1) and cryptoyunnanone I (2), were isolated from the leaves and twigs of Cryptocarya yunnanensis. Their structures were elucidated by the detailed spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Cryunchalcone (1) is a biflavonoid constructed by a dihydrochalcone coupled with a chalcone through an unprecedented C-2''-C-6 linkage. Cryptoyunnanone I (2) is a unique complex flavanone bearing a phenylpropanoid moiety.
Asunto(s)
Chalcona , Cryptocarya , Chalcona/química , Cryptocarya/química , Flavonoides/química , Estructura Molecular , Hojas de la Planta/químicaRESUMEN
An efficient divergent approach of Pd-catalyzed C-H oxygenation of polyaromatic rings is described. Reversible directing groups enable regiospecific peri- and ortho-oxygenation to readily access a wide array of polyaromatic phenols without pre- and postmanipulation of directing groups. The systematic mechanistic investigation, including deuterium-labeling experiments, palladacycle trapping, and DFT calculations, reveals that the tunable ligand-assisted C-H bond cleavage played a crucial role during the reaction process.