Synthesis and biological activity evaluation of novel peroxo-bridged derivatives as potential anti-hepatitis B virus agents. Issue 1 (4th November 2016)

• Record Type: Journal Article
• Authors: Jia, Menglu; Zhao, Rui; Xu, Bing; Yan, Wenqiang; Chu, Fuhao; Gu, Hongshun; Xie, Tianxin; Xiang, Hongjun; Ren, Jian; Chen, Dagang; Wang, Penglong; Lei, Haimin
• Is Part Of: MedChemComm. Volume 8:Issue 1(2017)
• Page Start: 148
• Page End: 151
• Publication Date: 2016-11-04
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c6md00344c
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Previous studies have demonstrated that natural steroid compounds containing a peroxide bridge exhibited potential anti-hepatitis B virus activity. 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 β-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, 5α, 8α-cyclicobioxygen-6-vinyl-3-oxo-cholesterone (1f, 3.13 μg 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 compound1f was 362.46 mg kg −1 after an intraperitoneal injection in mice. Moreover, structure–activity relationships of cholesterol and β-sitosterol derivatives were briefly discussed.