Citation: Zhu Li, Yang Yanqiu, Gao Peipei, An Xue, Sun Yingying, Sun Xiaowen, Hou Yue, Shan Lihong. Synthesis and Anti-inflammatory Activity Evaluation of 2-Dehydroepiandrosterone Benzene Methyl Derivatives[J]. Chinese Journal of Organic Chemistry, ;2019, 39(9): 2625-2631. doi: 10.6023/cjoc201901039 shu

Synthesis and Anti-inflammatory Activity Evaluation of 2-Dehydroepiandrosterone Benzene Methyl Derivatives

Zhu Li ^a,b ,
Yang Yanqiu ^c ,
Gao Peipei ^a,b ,
An Xue ^a,b ,
Sun Yingying ^a,b ,
Sun Xiaowen ^a,b ,
Hou Yue ^c,, ,
Shan Lihong ^a,b,,

a.
School of Pharmaceutical Sciences, Zhengzhou 450001
b.
Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001
c.
College of Life and Health Sciences, Northeastern University, Shenyang 110819

Corresponding author: Hou Yue, houyue@mail.neu.edu.cn Shan Lihong, shlh@zzu.edu.cn
Received Date: 25 January 2019
Revised Date: 22 March 2019
Available Online: 11 September 2019
Fund Project: Project supported by the National Natural Science Foundation of China (Nos. 21402178, U1603125) and the Scientific Research Fund of Henan Province (No. 132300410195)the National Natural Science Foundation of China 21402178the National Natural Science Foundation of China U1603125the Scientific Research Fund of Henan Province 132300410195

Figures(1)

Alzheimer's Disease (AD) is one of the major health crises in the 21st century, and due to the complexity of its pathogenesis, there has no good solution to cure this disease. In order to find more economical and effective drugs for the treatment of neurodegenerative diseases, a series of novel 2-dehydroepiandrosterone benzathine derivatives were synthesized and their activity on the NO release of microglia cell line BV-2 activated by lipopolysaccharide (LPS), as well as their effect on cell viability were studied. The structures of the synthesized compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. The results showed that all compounds had inhibitory effects on the NO release of LPS-activated mouse microglial cell line BV2 after 24 h of treatment, and it was dose-dependent. In particular, the IC₅₀ values of 2-(3-chloro)benzylidene-15β, 16β-methylene-androstane-4, 6-diene-3, 17-dione (5a) and 2-(3, 4, 5-trimethoxy)benzylidene-15β, 16β-methylene-androstane-4, 6-die-ne-3, 17-dione (5j) were 2.69 and 3.28 μmol·L^-1, respectively, which were better than the positive control Minocycline. The results showed that these compounds may be effective in the development of neurodegenerative diseases involving activation of microglia, and the mechanism deserved further study.
- dehydroepiandrosterone,
- chalcone analogue,
- alzheimer's disease,
- microglia
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