滇产南方红豆杉枝叶中紫杉烷二萜化学成分及其骨髓瘤细胞毒活性研究  

Study on the taxane diterpenoids in the branches and leaves of Taxus chinensis var.mairei from Yunnan Province and their myeloma cytotoxicity

作　　者：刘林 黄建宜 郭峰 臧浩景 郝小江[1] 邸迎彤[1] LIU Lin;HUANG Jian-yi;GUO Feng;ZANG Hao-jing;HAO Xiao-jiang;DI Ying-tong(Kunming Institute of Botany,Chinese Academy of Sciences,Kunming 650201,China;University of Chinese Academy of Sciences,Beijing 100049,China;Yunnan University of Chinese Medicine,Kunming 650500,China;College of Life Sciences,Yunnan University,Kunming 650504,China)

机构地区：[1]中国科学院昆明植物研究所,昆明650201 [2]中国科学院大学,北京100049 [3]云南中医药大学,昆明650500 [4]云南大学生命科学院,昆明650504

出　　处：《天然产物研究与开发》2024年第8期1320-1329,1349,共11页Natural Product Research and Development

基　　金：云南省科技厅项目(202201AS070040、202305AH340005、202302AA310035);DR PLANT项目。

摘　　要：为了研究滇产南方红豆杉中紫杉烷二萜类成分及其骨髓瘤细胞毒活性,运用正相、反相以及排阻色谱等分离手段对南方红豆杉枝叶提取物的化合物进行分离和纯化,通过NMR等波谱手段鉴定化合物结构,并采用CCK-8法分析化合物体外抑制NEK2过表达骨髓瘤细胞增殖作用。从该植物中分离鉴定了16个紫杉烷二萜类化合物,分别为13-肉桂酰基-1-脱羟基巴卡丁Ⅳ(1)、紫杉素(2)、5α-桂皮酰氧基-9α,10β,13α-三乙酰氧基紫杉-4(20),11-二烯(3)、紫杉宁E(4)、hongdoushan A(5)、11-diene-2α,5α,9α,10β,13β-pentol-2α,9α,10β,13α-tetraacetate-5α-cinnamate(6)、taxezopidine H(7)、紫杉素B(8)、taxuyunnanine C(9)、1-deoxybaccatin VI(10)、19-羟基巴卡丁III(11)、巴卡丁III(12)、7,9,13-三去乙酰基巴卡丁VI(13)、10-脱乙酰基巴卡丁III(14)、紫杉醇(15)、7-表紫杉醇(16),其中化合物1为新化合物,化合物5、13为首次从南方红豆杉中分离得到,化合物2、6、7、11有明显的抑制NEK2过表达骨髓瘤细胞增殖作用(IC 50=24.0、23.5、26.1、18.3μmol/L),化合物16的抑制作用尤为显著(IC 50=0.6μmol/L)。This study aims to investigate the taxane diterpenoid constituents of Taxus chinensis var.mairei from Yunnan Province and their myeloma cytotoxic activities.Compounds were isolated and purified from the extract of the leaves and branches of Taxus chinensis var.mairei by using normal-phase,reversed-phase and size exclusion chromatography,and their structures were identified by NMR spectroscopic methods.The isolated compounds were screened for activity against NEK2 over expression myeloma cell proliferation using a CCK-8 assay.Sixteen taxane diterpenoids were obtained and identified as 13-cinnamoyloxy-1-dehydroxy baccatin IV(1),taxusin(2),5α-cinnamoyloxy-9α,10β,13α-triacetoxytaxa-4(20),11-diene(3),7-deacetoxy taxinine J(4),hongdoushan A(5),11-diene-2α,5α,9α,10β,13β-pentol-2α,9α,10β,13α-tetraacetate-5α-cinnamate(6),taxezopidine H(7),taxinine B(8),taxuyunnanine C(9),1-deoxybaccatin VI(10),19-hydroxybaccatin III(11),baccatin III(12),7,9,13-trideacetyl baccatin VI(13),10-deacetylbaccatin III(14),taxol(15),7-epi-taxol(16).Compound 1 was a new taxane diterpenoid,while compounds 5 and 13 were isolated from Taxus chinensis var.mairei for the first time.The results indicated that compounds 2,6,7 and 11 had notable inhibitory activity on NEK2 over expression myeloma cell proliferation(IC 50=24.0,23.5,26.1,18.3μmol/L),and compound 16(IC 50=0.6μmol/L)had a significant effect.

关 键 词：南方红豆杉 紫杉烷二萜 骨髓瘤细胞 细胞毒 化学成分 

分 类 号：R284.1[医药卫生—中药学]