Active constituents of Zanthoxylum nitidium from Yunnan Province against leukaemia cells in vitro.

Active constituents of Zanthoxylum nitidium from Yunnan Province against leukaemia cells in vitro.
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DOI:
10.1186/s13065-021-00771-0
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发表时间:
2021-07-23
期刊:
影响因子:
4.6
通讯作者:
Mu S
Mu S
中科院分区:
化学2区
文献类型:
--
作者:
Deng Y;Ding T;Deng L;Hao X;Mu S

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花椒(Zanthoxylum nitidium)DC(芸香科)以抑制人类胃癌、肝癌、肾癌和肺癌细胞的增殖而闻名,尽管对其治疗白血病的潜在用途的研究相对较少。从花椒根和叶的氯仿和石油醚提取物中分离得到26个化合物。他们(+)9“-O-transferuloyl-5 5”-dimethoxylaricriresinol(1), 8 -(3“-oxobut-1”1“yl) 5, 7-dimethoxy-coumarin (2), 5, 7, 8-trimethoxy-coumarin (3), 5 - (3 ', 3 ' -dimethyl-2”8-dimethoxy-coumarin -butenyloxy) 7日,(4)、2 - (5-methoxy-2-methyl-1H-indol-3-yl)乙酸甲酯(5),2 ' - (5 6-dihydrochleletrythrine-6-yl)乙酸乙酯(6),6-acetonyldi-hydrochelerythrine(7) 6β-hydroxymethyldihydronitidine (8), bocconoline (9), zanthoxyline (10), O-methylzanthoxyline (11), rhoifoline B (12),n -去硝基丁(13)、硝基丁(14)、车车草碱(15)、4-羟基-7,8-二甲氧基-呋喃喹啉(16)、双胺胺(17)、γ-fagarine(18)、skimmianine(19)、robustine(20)、R-(+)-platydesmine(21)、4-甲氧基-1-甲基-2-喹啉(22)、4-甲氧基-2-喹诺酮(23)、liriodenine(24)、aurantiamide acetate(25)、10- o -demethyl-12- o -methyl nottianamide(26)。其中化合物4 ~ 6和16首次通过UV、IR、1D、2D NMR和HR-ESI-MS谱图得到证实。化合物1 ~ 2和11为首次从该植物中分离得到。化合物1、2、9、10、14、15和24对白血病细胞系HEL具有较好的抑制活性,而化合物14 (IC50: 3.59µM)和化合物24 (IC50: 15.95µM)表现出较强的抑制活性。因此,为了进一步探讨其可能的机制,我们进行了细胞周期和凋亡实验,结果表明化合物14在HEL细胞中引起明显的s期阻滞并诱导凋亡,而化合物24仅诱导凋亡。目前的结果表明,化合物14和24都是有潜力的抗白血病候选药物。在线版本包含补充材料,可在10.1186/s13065-021-00771-0获得。
Zanthoxylum nitidium (Roxb.) DC (Rutaceae) is well known for inhibiting the proliferation of human gastric, liver, kidney and lung cancer cells, though research on its potential use in treating leukaemia is relatively rare. Twenty-six compounds were isolated from the chloroform and petroleum ether extracts of the roots and leaves of Z. nitidium (Zanthoxylum nitidium). They were ( +)-9′-O-transferuloyl-5, 5′-dimethoxylaricriresinol (1), 8-(3′-oxobut-1′-en-1′-yl)-5, 7-dimethoxy-coumarin (2), 5, 7, 8-trimethoxy-coumarin (3), 5-(3′, 3′-dimethyl-2′-butenyloxy)-7, 8-dimethoxy-coumarin (4), 2-(5-methoxy-2-methyl-1H-indol-3-yl) methyl acetate (5), 2′-(5, 6-dihydrochleletrythrine-6-yl) ethyl acetate (6), 6-acetonyldi-hydrochelerythrine (7), 6β-hydroxymethyldihydronitidine (8), bocconoline (9), zanthoxyline (10), O-methylzanthoxyline (11), rhoifoline B (12), N-nornitidine (13), nitidine (14), chelerythrine (15), 4-hydroxyl-7,8-dimethoxy-furoquinoline (16), dictamnine (17), γ-fagarine (18), skimmianine (19), robustine (20), R-( +)-platydesmine (21), 4-methoxyl-1-methyl-2-quinoline (22), 4-methoxy-2-quinolone (23), liriodenine (24), aurantiamide acetate (25), 10-O-demethyl-12-O-methylarnottianamide (26). Four among them, compounds 4 – 6 and 16, were first confirmed in this study by UV, IR, 1D, 2D NMR and HR-ESI–MS spectra. Compounds 1 – 2 and 11 were isolated from Z. nitidium for the first time. Of the assayed compounds, 1, 2, 9, 10, 14, 15 and 24, exhibited good inhibitory activities in the leukaemia cell line HEL, whereas compound 14 (IC50: 3.59 µM) and compound 24 (IC50: 15.95 µM) exhibited potent inhibitory activities. So, to further investigate the possible mechanisms, cell cycle and apoptosis assays were performed, which indicated that compound 14 causes obvious S-phase arrest in HEL cells and induced apoptosis, whereas compound 24 only induced apoptosis. The present results suggested both compounds 14 and 24 are promising potential anti-leukaemia drug candidates. The online version contains supplementary material available at 10.1186/s13065-021-00771-0.
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