红大戟中的蒽醌类化学成分

Anthraquinones from the Roots of Knoxia valerianoides

目的:研究茜草科红芽大戟属植物红大戟根的化学成分,并对其在多种体外药理模型上进行了活性筛选。方法:运用硅胶、Sephadex LH-20柱色谱和制备薄层色谱等方法进行分离和纯化,通过理化性质和NMR,MS等波谱数据鉴定化合物的结构;在细胞水平模型上,筛选化合物在抗氧化、抗HIV、神经细胞保护及肿瘤细胞毒等方面的活性。结果:从95%乙醇提取物中分离鉴定了21个蒽醌类化合物,包括去甲虎刺醛(1)、1,3-二羟基-2-乙氧甲基-9,10-蒽醌(2)、甲基异茜草素(3)、虎刺醇(4)、1,3,5-三羟基-2-乙氧甲基-6-甲氧基-9,10-蒽醌(5)、3-羟基巴戟醌(6)、红大戟素(7)、1,3,5-三羟基-2-甲酰基-6-甲氧基-9,10-蒽醌(8)、芦西丁(9)、异茜草素(10)、1,3-二羟基-2-甲氧基-9,10-蒽醌(11)、1,3-二羟基-2-甲氧甲基-9,10-蒽醌(12)、1-羟基-2-羟甲基-9,10-蒽醌(13)、3-羟基-2-甲基-9,10-蒽醌(14)、3-羟基-1-甲氧基-2-甲基-9,10-蒽醌(15)、1,3-二羟基-2-乙氧甲基-6-甲氧基-9,10-蒽醌(16)、1,3,6-三羟基-2-甲基-9,10-蒽醌(17)、1,3-二羟基-2-羟甲基-6-甲氧基-9,10-蒽醌(18)、1,3,6-三羟基-2-甲氧甲基-9,10-蒽醌(19)、3,6-二羟基-2-羟甲基-9,10-蒽醌(20)和1,6-二羟基-2-甲基-9,10-蒽醌(21)。在1.0×10-5 mol.L-1浓度下,在肿瘤细胞(MTT法,HCT-8,Bel7402,BGC-823,A549,A2780)、去血清和谷氨酸损伤神经细胞、Fe2+-Cys诱导大鼠肝微粒体丙二醛生成和小鼠腹腔巨噬细胞分泌NO模型,以及抗HIV(VSVG/HIV-luc)和抗糖尿病(PTPB酶抑制)模型上,以上化合物均未显示出显著活性。结论:化合物9～21为首次从本属植物中分离得到。

Objective： To investigate the chemical constituents of the roots of Knoxia valerianoides and their biological activities. Method： The anthraquinones were isolated by using a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC. Structures of the isolates were identified by their physicalchemical properties and spectroscopic analysis including 2D NMR and MS. Antioxidant, anti-HIV, neuroprotective, and cytotoxic activities were screened by using cell-based models. Result： Twenty-two constituents were isolated from an ethanolic extract of the roots of K. valerianoides. Their structures were identified as nordamnacanthal（1）, ibericin（2）, rubiadin（3）, damnacanthol（4）, 2-ethoxymethylknoxiavaledin （ 5 ）, 3-hydroxymorindone （ 6 ）, knoxiadin （ 7 ）, 2 -formyl knoxiavaledin （ 8 ）, lucidin （ 9 ）, xanthopurpurin （ 10 ）, 1, 3-dihydroxy-2-methoxy-9, 10- anthraquinone （ 11 ）, lucidin （ -methyl ether（ 12）, digiferruginol （ 13）, 3-hydroxy-2-methyl-9, 10-anthraquinone （ 14）, rubiadin-l-methyl ether （ 15 ）, 6-methoxylucidin （ -ethyl ether （ 16 ）, 1, 3, 6-trihydroxy-2-methyl-9, 10-anthraquinone （ 17）, 1, 3-dihydroxy-2-hydroxy methyl-6-methoxy-9, 10-anthraquinone（ 18）, 1, 3, 6-trihydroxy-2-methoxymethyl-9, 10- anthraquinone （19）, 3, 6-dihydroxy-2- hydroxymethyl-9, lO-anthraquinone（20）, and 1, 6-dihydroxy-2-methyl-9, 10-anthra quinone （21）. In the in vitro assays, at a concentration of 1 ×10^-5 mol ·L^-1, no compounds were active against human cancer cell lines （HCT-8, Be17402, BGC-823, A549, and A2780）, deserum and glutamate induced PC12-syn cell damage, LPS induced NO production in macrophage, Fe2＋ -cystine induced rat liver microsomal lipid peroxidation, HIV-1 replication, and protein tyrosine phosphatase 1B （PTP1B）. Conclusion： Compounds 9-21 were obtained from the roots of K. valerianoides for the first time.