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Diterpenoids from Euphorbia royleana reverse P-glycoprotein-mediated multidrug resistance in cancer cells
Phytochemistry ( IF 3.2 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.phytochem.2020.112395 Sharpkate Shaker 1 , Jun Sang 1 , Xue-Long Yan 1 , Run-Zhu Fan 1 , Gui-Hua Tang 1 , You-Kai Xu 2 , Sheng Yin 1
Phytochemistry ( IF 3.2 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.phytochem.2020.112395 Sharpkate Shaker 1 , Jun Sang 1 , Xue-Long Yan 1 , Run-Zhu Fan 1 , Gui-Hua Tang 1 , You-Kai Xu 2 , Sheng Yin 1
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Eight previously undescribed diterpenoids, euphoroyleans A-H, including two cembranes, three ingenanes, two ent-atisanes, and one ent-kaurane, along with 22 known analogues were isolated from the whole plants of Euphorbia royleana. The structures of euphoroyleans A-H, including the absolute configurations, were elucidated by extensive spectroscopic analyses, chemical transformation, and single crystal X-ray diffractions. All the isolates were screened for their chemoreversal abilities on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) cancer cell line HepG2/DOX, and eight compounds exhibited significant activities. Among them, ingol-3,7,12-triacetate-8-benzoate, the most active MDR modulator with no obvious cytotoxicity, could enhance the efficacy of anticancer drug DOX to ca. 105 folds at 10 μM, being stronger than the positive drug verapamil. Mechanistic study revealed that ingol-3,7,12-triacetate-8-benzoate could inhibit the transport activity of P-gp rather than its expression, and the possible recognition mechanism between compounds and P-gp was predicted by molecular docking.
中文翻译：
来自大戟的二萜类化合物逆转癌细胞中 P-糖蛋白介导的多药耐药性
从 Euphorbia royleana 的整个植物中分离出 8 种以前未描述的二萜类物质，即大戟类 AH，包括两种 cembranes、三种 ingenanes、两种 ent-atisanes 和一种 ent-kaurane，以及 22 种已知的类似物。euphoroyleans AH 的结构，包括绝对构型，通过广泛的光谱分析、化学转化和单晶 X 射线衍射阐明。筛选了所有分离株对 P-糖蛋白 (P-gp) 介导的多药耐药 (MDR) 癌细胞系 HepG2/DOX 的化学逆转能力，并且八种化合物表现出显着的活性。其中，ingol-3,7,12-triacetate-8-benzoate 是最活跃的 MDR 调节剂，无明显细胞毒性，可将抗癌药物 DOX 的疗效提高至约 10 μM 105 倍，比阳性药物维拉帕米更强。机理研究表明，ingol-3,7,12-triacetate-8-benzoate 可以抑制 P-gp 的转运活性而不是其表达，通过分子对接预测化合物与 P-gp 之间可能的识别机制。
更新日期：2020-08-01
中文翻译：
来自大戟的二萜类化合物逆转癌细胞中 P-糖蛋白介导的多药耐药性
从 Euphorbia royleana 的整个植物中分离出 8 种以前未描述的二萜类物质，即大戟类 AH，包括两种 cembranes、三种 ingenanes、两种 ent-atisanes 和一种 ent-kaurane，以及 22 种已知的类似物。euphoroyleans AH 的结构，包括绝对构型，通过广泛的光谱分析、化学转化和单晶 X 射线衍射阐明。筛选了所有分离株对 P-糖蛋白 (P-gp) 介导的多药耐药 (MDR) 癌细胞系 HepG2/DOX 的化学逆转能力，并且八种化合物表现出显着的活性。其中，ingol-3,7,12-triacetate-8-benzoate 是最活跃的 MDR 调节剂，无明显细胞毒性，可将抗癌药物 DOX 的疗效提高至约 10 μM 105 倍，比阳性药物维拉帕米更强。机理研究表明，ingol-3,7,12-triacetate-8-benzoate 可以抑制 P-gp 的转运活性而不是其表达，通过分子对接预测化合物与 P-gp 之间可能的识别机制。
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