中文名称:

臭椿酮

中文同义词:

臭椿酮(臭椿苦酮);臭椿酮;AILANTHONE 臭椿酮;臭椿酮对照品

英文名称:

ailanthone

英文同义词:

11β,20-Epoxy-1β,11,12α-trihydroxypicrasa-3,13(21)-diene-2,16-dione;13,21-Didehydrochaparrinone;ailanthone;Picrasa-3,13(21)-diene-2,16-dione,11,20-epoxy-1,11,12-trihydroxy-, (1b,11b,12a)-;(1β,11β,12α)-11,20-Epoxy-1,11,12-trihydroxypicrasa-3,13(21)-diene-2,16-dione;Δ13-Dehydrochaparrinone;Picrasa-3,13(21)-diene-2,16-dione, 11,20-epoxy-1,11,12-trihydroxy-, (1β,11β,12α)-

CAS号:

981-15-7

分子式:

C20H24O7

分子量:

376.4

EINECS号:

相关类别:

标准品;植物提取物;中药对照品;对照品;精细化工;二萜;标准品 -中药标准品;Diterpenoids

Mol文件:

981-15-7.mol

熔点 

235-237 °C

沸点 

641.0±55.0 °C(Predicted)

密度 

1.47

储存条件 

Sealed in dry,Store in freezer, under -20°C

酸度系数(pKa)

11.85±0.70(Predicted)

植物提取物

臭椿酮是一种植物提取物，是从臭椿皮中提取出来的一种物质，具有抗菌、抗原虫及抗肿瘤作用，100%煎剂在体外对福氏痢疾杆菌、宋氏痢疾杆菌和大肠杆菌有抑制作用。对阿米巴原虫与阴道滴虫有强烈的抑制作用，并能抑制其它寄生虫的活动，煎液与鞣质有收敛、止血作用。 臭椿酮对人体鼻咽癌（KB）细胞有细胞毒活性，其ED50为10-2-10-3ug/ml在0.12-4.00mg/kg剂量时，对淋巴细胞白血病P388显示一定活性。 臭椿皮为植物苦木科臭椿的根皮或树皮。主产於山东省、辽宁省、河南省、安徽省等地。春夏采挖，除去栓皮，切片，晒干，生用，亦用鲜品。

制备方法

取臭椿新鲜树皮或者新鲜根皮，加入其质量5-10倍量体积pH＝9-13的碱水浸泡24-72小时，滤过，滤液用酸调节pH至中性，浓缩，浓缩液通过大孔吸附树脂柱吸附，水洗脱除杂，60-85％乙醇洗脱，收集3-8倍量柱体积洗脱液，减压回收乙醇至尽，冷藏12-36小时析晶，滤过，取滤渣，加入丙酮重结晶，洗涤、干燥即得臭椿酮。

生物活性

Ailanthone (AIL, Δ13-Dehydrochaparrinone) 是一种来自臭椿Ailanthus altissima的天然通过抗肝癌(HCC)成分，可通过降低 cyclins 和 CDKs 的表达、提高 p21 和 p27 的表达来诱导G0/G1期细胞周期阻滞。Ailanthone 可触发DNA损伤，其特征为 ATM/ATR 通路的激活。Ailanthone 可在Huh7细胞中诱导线粒体介导、涉及 PI3K/AKT 信号通路的细胞凋亡。Ailanthone 也是全长 Androgen Receptor (AR-FL)和组成型活性截断AR剪接变体(AR-Vs, AR1-651)的抑制剂，对应的IC50值分别为69 nM和309 nM。

靶点

Target Value CDK () AR-FL (Cell-free assay) 69 nM AR 1-651 (Cell-free assay) 309 nM

Target

Value

CDK ()

AR-FL (Cell-free assay)

69 nM

AR 1-651 (Cell-free assay)

309 nM

体外研究

Ailanthone is a potent inhibitor of both full-length AR (AR-FL) and constitutively active truncated AR splice variants (AR-Vs). Ailanthone binds to the co-chaperone protein p23 and prevents ARs interaction with HSP90, thus resulting in the disruption of the AR-chaperone complex followed by ubiquitin/proteasome-mediated degradation of AR as well as other p23 clients including AKT and Cdk4, and downregulates AR and its target genes in PCa cell lines and orthotopic animal tumours. In addition, Ailanthone blocks tumour growth and metastasis of CRPC. Ailanthone has been shown to possess an growth-inhibitory effect against several cancer cell lines including HepG2, Hep3B, R-HepG2, Jurkat, HeLa, MCF-7, MDA-MB-231 and A549 cells. Ailanthone inhibits Huh7 cell growth through the induction of mitochondrion-mediated cell apoptosis and G0/G1 cell cycle arrest. Ailanthone-induced apoptosis is mitochondrion-mediated and involved the PI3K/AKT signaling pathway in Huh7 cells.

体内研究

Not only i.p. administration but also p.o. administration of Ailanthone has excellent efficiency for blocking the growth of CRPC xenografts. In pharmacokinetic studies, Ailanthone exhibits good solubility in water and good bioavailability (>20%). In addition, Ailanthone effectively suppresses CRPC tumour growth, despite not reaching a steady state of plasma drug concentration during the course of treatment.