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玛莱雅美登木中新的葫芦素衍生物对肝癌的抗增殖活性

Liver cancer antiproliferative activity of a new nor-cucurbitacin from Mareya micrantha Müll. Arg.

机构信息

Laboratoire de Constitution et Réaction de la Matière (LCRM), UFR-SSMT, Université Félix Houphouët-Boigny, 22 BP 582 Abidjan 22, Côte d'Ivoire.

Laboratoire des Procédés Industriels de Synthèse, de l'Environnement et des Energies Nouvelles (LAPISEN), INP-HB Yamoussoukro, BP 1093 Yamoussoukro, Côte d'Ivoire.

出版信息

Fitoterapia. 2023 Apr;166:105471. doi: 10.1016/j.fitote.2023.105471. Epub 2023 Mar 12.

Abstract

Mareya micrantha Müll. Arg. (Euphorbiaceae) is a plant used in the Ivorian traditional medicinal system for various medical properties such as laxative, oxytocic, intestinal infectious diseases, malaria, etc. Six cucurbitacin derivatives (tetracyclic triterpenoids) are isolated from the leaves, stem barks or root barks of M. micrantha. Among these compounds, 29-nor-2β,15α,20β-trihydroxy-16α-acetyl-3,1,22-trioxo-cucurbita-4,23-diene (1) is a new nor-cucurbitacin isolated from the leaves; 29-nor-1,2,3,4,5,10-dehydro-3,15α,20β-trihydroxy-16α-acetyl-11,22-dioxo-cucurbita-23-ene 2-O-β-D-glucopyranoside (2) and 29-nor-2β,15α,20β-trihydroxy-16α-acetyl-3,11,22 trioxo-cucurbita-4,23-diene 2-O-β-D glucopyranoside (3) are new nor-cucurbitacins recently discovered by us in leaves and isolated again for this study while dihydro-epi-isocucurbitacin D (4), tetrahydro-cucurbitacin I (5) and cucurbitacin L (6) are known cucurbitacins but newly isolated from the stem barks and the root barks of M. micrantha. Their chemical structures are established according to spectral data (UV, IR, MS and H, C NMR). Their antiproliferative activity is explored in vitro on the chemo-resistant human hepatocarcinoma cell line Hep3B. Compound 1 showed a strong and selective antiproliferative activity against this cancer cell line (IC value of 0.12 ± 0.05 μM) when compared to normal hepatocytes HepaRG.

摘要

玛莱雅小冠木(Mareya micrantha Müll. Arg.)(大戟科)是一种植物,在科特迪瓦传统医学体系中用于各种医疗特性,如通便、催产、肠道传染病、疟疾等。从小冠木的叶子、茎皮或根皮中分离出六种葫芦素衍生物(四环三萜)。在这些化合物中,29-降-2β,15α,20β-三羟基-16α-乙酰基-3,1,22-三氧代-瓜-4,23-二烯(1)是从叶子中分离出来的一种新的降葫芦素;29-降-1,2,3,4,5,10-脱氢-3,15α,20β-三羟基-16α-乙酰基-11,22-二氧代-瓜-23-烯 2-O-β-D-吡喃葡萄糖苷(2)和 29-降-2β,15α,20β-三羟基-16α-乙酰基-3,11,22 三氧代-瓜-4,23-二烯 2-O-β-D-吡喃葡萄糖苷(3)是我们最近在叶子中发现的新的降葫芦素,并再次分离出来进行这项研究,而二氢-表异葫芦素 D(4)、四氢葫芦素 I(5)和葫芦素 L(6)是已知的葫芦素,但却是新从玛莱雅小冠木的茎皮和根皮中分离出来的。根据光谱数据(UV、IR、MS 和 H、C NMR)确定了它们的化学结构。在体外对耐化疗的人肝癌细胞系 Hep3B 进行了它们的抗增殖活性研究。与正常肝细胞 HepaRG 相比,化合物 1 对这种癌细胞系表现出强烈而选择性的抗增殖活性(IC 值为 0.12±0.05μM)。

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