Synthesis and biological activity evaluation of novel peroxo-bridged derivatives as potential anti-hepatitis B virus agents.

ABSTRACT: Previous studies have demonstrated that natural steroid compounds containing a peroxide bridge exhibited potential anti-hepatitis B virus activity. To continue our research, a simple and regioselective methodology, using Eosin Y as a clean photosensitized oxidation catalyst, was developed for the synthesis of a peroxide bridge in steroids. The method that using Eosin Y as the catalyst was exposed to visible light and furbished in high yields, did not involve tedious work-up or purification, and avoided using environmentally hazardous solvents. It can be regarded as a green protocol. Moreover, a series of cholesterol and ?-sitosterol derivatives containing a peroxide bridge were synthesized using this method and screened for their anti-HBV activity. Among the compounds synthesized in this research, 5?,8?-cyclicobioxygen-6-vinyl-3-oxo-cholesterone (1f, 3.13 ?g ml^-1) had the most potent activity with inhibition rates of 77.45% ± 6.01% and 58.73% ± 8.64% on the secretion of HBsAg and HBeAg antigens, respectively, after 8 days. Further acute toxicity test showed that the LD₅₀ value of compound 1f was 362.46 mg kg^-1 after an intraperitoneal injection in mice. Moreover, structure-activity relationships of cholesterol and ?-sitosterol derivatives were briefly discussed.

SUBMITTER: Jia M 

PROVIDER: S-EPMC6072307 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature