Synthesis of <italic style="font-style: italic">α</italic>-mangostin derivatives and evaluation of  their inhibitory activities towards phosphodiesterase 4

DENG Jinhui; HUANG Yue; LIANG Jinhao; ZHU Jiaqi; YU Si; LIU Haobai; LUO Haibin; HUANG Yiyou; HE Xixin

doi:10.13471/j.cnki.acta.snus.2021C002

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Synthesis of α-mangostin derivatives and evaluation of their inhibitory activities towards phosphodiesterase 4

Research articles | 更新时间：2023-11-01

- Synthesis of α-mangostin derivatives and evaluation of their inhibitory activities towards phosphodiesterase 4
- Acta Scientiarum Naturalium Universitatis Sunyatseni Vol. 61, Issue 3, Pages: 53-61(2022)
- 作者机构：
  
  1.广州中医药大学中药学院，广东广州 510006
  2.中山大学药学院，广东广州 510006
- 作者简介：
- 基金信息：
- DOI：10.13471/j.cnki.acta.snus.2021C002
  CLC： R914.5
- Published：25 May 2022，
  
  Published Online：05 June 2021，
  
  Received：08 February 2021，
  
  Accepted：28 April 2021
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邓金辉,黄悦,梁津豪等.α-倒捻子素衍生物合成及其抑制磷酸二酯酶4活性研究[J].中山大学学报(自然科学版),2022,61(03):53-61.

DENG Jinhui,HUANG Yue,LIANG Jinhao,et al.Synthesis of α-mangostin derivatives and evaluation of their inhibitory activities towards phosphodiesterase 4[J].Acta Scientiarum Naturalium Universitatis Sunyatseni,2022,61(03):53-61.
邓金辉,黄悦,梁津豪等.α-倒捻子素衍生物合成及其抑制磷酸二酯酶4活性研究[J].中山大学学报(自然科学版),2022,61(03):53-61. DOI： 10.13471/j.cnki.acta.snus.2021C002.

DENG Jinhui,HUANG Yue,LIANG Jinhao,et al.Synthesis of α-mangostin derivatives and evaluation of their inhibitory activities towards phosphodiesterase 4[J].Acta Scientiarum Naturalium Universitatis Sunyatseni,2022,61(03):53-61. DOI： 10.13471/j.cnki.acta.snus.2021C002.

摘要

以

α-

倒捻子素为先导化合物设计合成一系列衍生物并测试其对磷酸二酯酶4 （PDE4，phosphodiesterase 4）的抑制活性。首先

α-

倒捻子素在DDQ作用下氧化环合得到中间体

，然后经烷基化、还原、水解、酰化等化学反应合成6-位取代的目标化合物；采用［

H］标记液体闪烁计数法测试了衍生物体外抑制PDE4活性。最终设计、合成了11个目标化合物，其结构经

H NMR、

C NMR、HRMS等波谱数据分析确证。活性测试结果表明7个化合物（

、

和

）的PDE4抑制活性强于

-倒捻子素，其中化合物

的活性最强（IC

=247 nmol/L）。

Abstract

Derivatives of

-mangostin were designed and synthesized in this study，and their phosphodiesterase 4（PDE4） inhibitory activities were evaluated

in vitro

．The initial substrate

-mangostin was converted into the cyclized compound

， followed by eleven desired compounds were prepared by alkylation， hydrolysis， acylation reaction and other methods. The structures of the desired compounds were confirmed by

H NMR，

C NMR and ESI-（HR）MS. The PDE4 inhibitory activities of these compounds were evaluated

in vitro

by ［

H］ liquid scintillation counting method. Among the desired compounds， compounds

，

and

showed stronger PDE4 inhibition activity than

-mangostin. Compound

exhibited potential PDE4 inhibitory activity with the IC

values of 247 nmol/L.

关键词

α-倒捻子素衍生物磷酸二酯酶4抑制剂

Keywords

α-mangostinderivativesphosphodiesterase 4（PDE4）inhibitor

references

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YIN Q， WU Y J， PAN S， et al. Activation of cholinergic anti-inflammatory pathway in peripheral immune cells involved in therapeutic actions of α-mangostin on collagen-induced arthritis in rats［J］. Drug Design， Development and Therapy， 2020，14：1983-1993.

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Synthesis of α-mangostin derivatives and evaluation of their inhibitory activities towards phosphodiesterase 4

DOI：10.13471/j.cnki.acta.snus.2021C002

摘要

Abstract

关键词

Keywords

references