文献类型：期刊文献

中文题名：新型漆酚基异羟肟酸衍生物的合成及HDAC抑制活性研究

英文题名：Synthesis and HDAC Inhibitory Activity of Novel Urushiol Hydroxamic Acid Derivatives

作者：周昊[1,2] 齐志文[1,2] 陶冉[1,2] 陈虹霞[1,2] 王成章[1,2]

第一作者：周昊

机构：[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

年份：2020

卷号：40

期号：1

起止页码：106-112

中文期刊名：林产化学与工业

外文期刊名：Chemistry and Industry of Forest Products

收录：CSTPCD;;Scopus;北大核心:【北大核心2017】；CSCD:【CSCD2019_2020】；

基金：国家自然科学基金资助项目(31600467)

语种：中文

中文关键词：漆酚;异羟肟酸衍生物;HDAC抑制剂

外文关键词：urushiol;hydroxamic acid derivatives;HDAC inhibitor

分类号：TQ35

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1 H 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(HDAC2)的作用模式,结果表明:3种化合物均能很好地与HDAC2的活性口袋结合,可与氨基酸(His145、Tyr308、Glu103和Asp104等)残基形成氢键相互作用,并能与活性口袋底部的Zn^2+形成稳定螯合。采用试剂盒AK-501检测化合物对HDAC2的抑制活性,结果表明:化合物2和3对HDAC2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IC 50分别为0.33,0.29和0.24 mg/L。
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,13C NMR and MS analysis.The interaction mode between the compounds and HDAC2 was studied by molecular docking.The results showed that three compounds could bind to the active pocket of HDAC2 and interact with the residues of His145,Tyr308,Glu103 and Asp104 to form hydrogen bonds.It could form stable chelation with Zn^2+ at the bottom of active pocket.The inhibitory activity of compounds on HDAC2 was detected by kit AK-501.The results showed that the inhibitory effects of compound 2 and 3 on HDAC2 were better than that of compound 1,and the IC50 values of compound 2 and 3 were similar to that of SAHA(IC 50=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.