中药两面针的化学成分及细胞毒活性成分研究Chemical and cytotoxic constituents of Zanthoxylum nitidum
赵丽娜,王佳,汪哲,谭宁华
ZHAO Li-na,WANG Jia,WANG Zhe,TAN Ning-hua
摘要(Abstract)：
采用硅胶、凝胶、RP-18中压柱色谱、HPLC等分离方法,结合NMR,MS等波谱技术,从中药两面针的甲醇提取物中分离鉴定了10个化合物,分别为zanthonitidine B(1)、cyclo-(Leu-Leu-Leu-Leu-Ile)(2)、6S-10-O-demethylbocconoline(3)、鹅掌楸碱(liriodenine,4)、异阔果芸香碱(isoplatydesmine,5)、5,5′-二甲氧基落叶松脂醇(5, 5′-dimethoxylariciresinol,6)、丁香树脂醇(syringaresinol,7)、表丁香脂素(episyringaresinol,8)、异紫花前胡内酯(marmesin,9)、丁香醛(syringaldehyde,10)。其中化合物1为新的生物碱类化合物,化合物2为首次从植物界发现的环五肽,化合物3为首次从花椒属植物中分离得到的生物碱。化合物3和4对人结肠癌细胞HT29、人非小细胞肺癌细胞A549和人乳腺癌细胞MDA-MB-231均具有一定的细胞毒活性,其IC_(50)分别为27.37, 24.10, 33.58μmol·L~(-1)和9.12, 6.05, 11.35μmol·L~(-1)。
Ten compounds were isolated from the methanol extract of Zanthoxylum nitidum through silica gel, Sephadex LH-20, RP-18 and HPLC chromatography techniques. Their structures were elucidated by the MS and NMR spectra as zanthonitidine B(1), cyclo-(Leu-Leu-Leu-Leu-Ile)(2),6S-10-O-demethylbocconoline(3), liriodenine(4), isoplatydesmine(5), 5, 5′-dimethoxylariciresinol(6), syringaresinol(7), episyringaresinol(8), marmesin(9) and syringaldehyde(10). Among them,1 is a new alkaloid,2 is a cyclopentapeptide isolated from plant kingdom for the first time, and 3 is from the genus Zanthoxylum for the first time. Compounds 3 and 4 exhibited cytoxoxicity against three human cancer cell lines HT29, A549 and MDA-MB-231 with IC_(50) values of 27.37, 24.10, 33.58 μmol·L~(-1) and 9.12,6.05, 11.35 μmol·L~(-1),respectively.
关键词(KeyWords)：
花椒属;两面针;生物碱;环肽;细胞毒活性
Zanthoxylum;Zanthoxylum nitidum;alkaloids;cyclopeptides;cytotoxicity
基金项目(Foundation): 国家自然科学基金面上项目(31470428);; 江苏省“双创团队”项目;; 中国药科大学高层次人才引进项目
作者(Author):
赵丽娜,王佳,汪哲,谭宁华
ZHAO Li-na,WANG Jia,WANG Zhe,TAN Ning-hua
参考文献(References)：
- [1] 中国药典.一部[S]. 2015: 169.
- [2] 黄琪, 雷鹏, 欧阳冬生. 芸香科花椒属植物两面针抗肿瘤作用研究进展[J]. 肿瘤药学, 2011, 1(6): 482.
- [3] 冯燕英,刘华钢,梁燕,等.氯化两面针碱对人卵巢癌紫杉醇耐药细胞株A2780 Taxol细胞耐药性的逆转作用[J].中国实验方剂学杂志,2015,21(13):95.
- [4] 廖柳凤,欧贤红,刘华钢,等.氯化两面针碱对MCF-7细胞增殖的抑制及对P125表达的影响[J].中国实验方剂学杂志,2016,22(19):85.
- [5] Zhao L N, Guo X X, Liu S, et al. (±)-Zanthonitidine A, a pair of enantiomeric furoquinoline alkaloids from Zanthoxylum nitidum with antibacterial activity [J]. Nat Prod Bioprospecting, 2018,8:361.
- [6] 周俊, 谭宁华. 植物环肽的薄层化学识别新方法及其在植物化学研究中的应用 [J]. 科学通报, 2000, 45(20): 1047.
- [7] Talontsi F M, Facey P, Tatong M D K, et al. Zoosporicidal metabolites from an endophytic fungus Cryptosporiopsis sp. of Zanthoxylum leprieurii [J]. Phytochemistry, 2012, 83(3): 87.
- [8] Sukieum S, Sangaroon W, Yenjai C. Coumarins and alkaloids from the roots of Toddalia asiatica [J]. Nat Prod Res, 2018, 32(1): 944.
- [9] Pang S Q, Wang G Q, Huang B K, et al. Isoquinoline alkaloids from Broussonetia papyrifera fruits [J]. Chem Nat Compd, 2007, 43(1): 100.
- [10] Chen J J, Chang Y L, Teng C M, et al. Quinoline alkaloids and anti-platelet aggregation constituents from the leaves of Melicope semecarpifolia [J]. Planta Med, 2002, 68(9): 790.
- [11] 冯煦, 董云发, 王鸣, 等. 臭常山喹啉生物碱成分 [J]. 中草药, 2004, 35(12): 1336.
- [12] Ida Y, Saton Y, Ohtsuka M, et al. Phenolic constituents of Phellodendron amurense bark [J]. Phytochemistry, 1993, 35(1): 209.
- [13] Kwon H C, Choi S U, Lee J O, et al. Two new lignans from Lindera obtusiloba Blume [J]. Arch Pharm Res, 1999, 22(4): 417.
- [14] 丛悦, 王艳, 王天晓, 等. 功劳木的化学成分研究[J]. 中成药, 2011, 33(6): 1008.
- [15] 肖瑛,李建北,丁怡.毛大丁草根茎化学成分的研究[J].中国中药杂志,2002,27(8):594.
- [16] Zhang X, Gao H, Wang N L, et al. Phenolic components from Dendrobium nobile [J]. Chin Trad Herb Drugs, 2006, 37(5): 652.