新型漆酚基异羟肟酸衍生物的合成及HDAC抑制活性研究

doi:10.3969/j.issn.0253-2417.2020.01.015

林产化学与工业 ›› 2020, Vol. 40 ›› Issue (1): 106-112.doi: 10.3969/j.issn.0253-2417.2020.01.015

新型漆酚基异羟肟酸衍生物的合成及HDAC抑制活性研究

周昊^1,²,齐志文^1,²,陶冉^1,²,陈虹霞^1,²,王成章^1,^2,*()

1. 中国林业科学研究院林产化学工业研究所; 生物质化学利用国家工程实验室; 国家林业和草原局林产化学工程重点实验室; 江苏省生物质能源与材料重点实验室, 江苏南京 210042
2. 南京林业大学江苏省林业资源高效加工利用协同创新中心, 江苏南京 210037

收稿日期:2019-05-22 出版日期:2020-02-28 发布日期:2020-03-06
通讯作者: 王成章 E-mail:wangczlhs@sina.com
作者简介:周昊(1982-),女,江苏盐城人,副研究员,硕士,主要从事天然产物化学与利用研究
基金资助:
国家自然科学基金资助项目(31600467)

Synthesis and HDAC Inhibitory Activity of Novel Urushiol Hydroxamic Acid Derivatives

Hao ZHOU^1,²,Zhiwen QI^1,²,Ran TAO^1,²,Hongxia CHEN^1,²,Chengzhang WANG^1,^2,*()

1. Institute of Chemical Industry of Forest Products, CAF; National Engineering Lab. for Biomass Chemical Utilization; Key Lab. of Chemical Engineering of Forest Products, National Forestry and Grassland Administration; Key Lab. of Biomass Energy and Material, Jiangsu Province, Nanjing 210042, China
2. Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing 210037, China

Received:2019-05-22 Online:2020-02-28 Published:2020-03-06
Contact: Chengzhang WANG E-mail:wangczlhs@sina.com
Supported by:
国家自然科学基金资助项目(31600467)

摘要/Abstract

摘要：

以漆酚为原料，通过对其邻二酚羟基进行醚化反应，在其侧链尾部引入异羟肟酸基团，在苯环或脂肪链引入硝基、羟基等官能团，合成了3种新型亚甲基醚漆酚异羟肟酸衍生物，分别是亚甲基醚漆酚异羟肟酸（化合物1）、8'-羟基亚甲基醚漆酚异羟肟酸（化合物2）和6-硝基亚甲基醚漆酚异羟肟酸（化合物3）。用¹H NMR，¹³C NMR和MS等方法对所合成的化合物进行结构表征。采用分子对接研究了化合物与组蛋白去乙酰化酶-2（HDAC 2）的作用模式，结果表明：3种化合物均能很好地与HDAC 2的活性口袋结合，可与氨基酸（His145、Tyr 308、Glu103和Asp104等）残基形成氢键相互作用，并能与活性口袋底部的Zn²⁺形成稳定螯合。采用试剂盒AK-501检测化合物对HDAC 2的抑制活性，结果表明：化合物2和3对HDAC 2的抑制效果要优于化合物1，其半数抑制质量浓度（IC₅₀）值和阳性药SAHA（0.20 mg/L）的相当，化合物1，2和3对HDAC 2的IC₅₀分别为0.33，0.29和0.24 mg/L。

关键词: 漆酚, 异羟肟酸衍生物, HDAC抑制剂

Abstract:

Urushiol was used as raw material, through etherification of o-diphenol hydroxyl group, introducing isoxamic acid group into the tail of side chain, and functional groups of nitro, hydroxyl group into benzene ring or aliphatic chain. Three novel methylene ether urushiol hydroxamic acid derivatives were synthesized. The structure of the synthesized compounds was characterized by means of ¹H NMR, ¹³ C NMR and MS analysis. The interaction mode between the compounds and HDAC 2 was studied by molecular docking. The results showed that three compounds could bind to the active pocket of HDAC 2 and interact with the residues of His145, Tyr 308, Glu103 and Asp104 to form hydrogen bonds. It could form stable chelation with Zn²⁺ at the bottom of active pocket. The inhibitory activity of compounds on HDAC 2 was detected by kit AK-501. The results showed that the inhibitory effects of compound 2 and 3 on HDAC 2 were better than that of compound 1, and the IC₅₀ values of compound 2 and 3 were similar to that of SAHA(IC₅₀=0.20 mg/L), the half inhibitory concentrations (IC₅₀) of compounds 1, 2 and 3 on HDAC2 were 0.33, 0.29 and 0.24 mg/L, respectively.

Key words: urushiol, hydroxamic acid derivatives, HDAC inhibitor

中图分类号:

TQ35

周昊,齐志文,陶冉,陈虹霞,王成章. 新型漆酚基异羟肟酸衍生物的合成及HDAC抑制活性研究[J]. 林产化学与工业, 2020, 40(1): 106-112.

Hao ZHOU,Zhiwen QI,Ran TAO,Hongxia CHEN,Chengzhang WANG. Synthesis and HDAC Inhibitory Activity of Novel Urushiol Hydroxamic Acid Derivatives[J]. Chemistry and Industry of Forest Products, 2020, 40(1): 106-112.

图/表 4

参考文献 15

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新型漆酚基异羟肟酸衍生物的合成及HDAC抑制活性研究

Synthesis and HDAC Inhibitory Activity of Novel Urushiol Hydroxamic Acid Derivatives

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