环状和支链酰基链半乳糖甘油酯及其对抗肿瘤促进活性的影响。

Cyclic and branched acyl chain galactoglycerolipids and their effect on anti-tumor-promoting activity.

作者信息

Colombo Diego, Franchini Laura, Toma Lucio, Ronchetti Fiamma, Tanaka Reiko, Takayasu Junko, Nishino Hoyoku, Tokuda Harukuni

机构信息

Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università di Milano, Via Saldini 50, 20133 Milano, MI, Italy.

出版信息

Eur J Med Chem. 2006 Dec;41(12):1456-63. doi: 10.1016/j.ejmech.2006.07.007. Epub 2006 Sep 22.

DOI:10.1016/j.ejmech.2006.07.007

PMID:16996658

Abstract

Fifteen new galactoglycerolipid analogues, in which one or two branched, alicyclic or aromatic acyl chains are linked to 2-O-beta-D-galactosylglycerol (6'-position or 1,6' positions), were prepared and tested for their anti-tumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus early antigen (EBV-EA) activation. All compounds were active in inhibiting the EBV activation promoted by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), the branched compounds resulting in the most active glycoglycerolipid analogues of the series. The branched 2-O-[6-O-(3-methylbutanoyl)-beta-D-galactopyranosyl]-sn-glycerol (1a) and the structurally related alicyclic 2-O-[6-O-(2-cyclohexylethanoyl)-beta-D-galactopyranosyl]-sn-glycerol (1d), when tested in an in vivo two-stage carcinogenesis test, exhibited inhibitory effects on mouse skin tumor promotion.

摘要

制备了15种新的半乳糖甘油酯类似物，其中一个或两个支链、脂环族或芳香族酰基链连接到2-O-β-D-吡喃半乳糖基甘油（6'-位或1,6'-位），并使用针对爱泼斯坦-巴尔病毒早期抗原（EBV-EA）激活的短期体外试验测试了它们的抗肿瘤促进活性。所有化合物在抑制由肿瘤促进剂12-O-十四烷酰佛波醇-13-乙酸酯（TPA）促进的EBV激活方面均具有活性，支链化合物产生了该系列中活性最高的糖脂类似物。支链的2-O-[6-O-(3-甲基丁酰基)-β-D-吡喃半乳糖基]-sn-甘油（1a）和结构相关的脂环族2-O-[6-O-(2-环己基乙酰基)-β-D-吡喃半乳糖基]-sn-甘油（1d），在体内两阶段致癌试验中进行测试时，对小鼠皮肤肿瘤促进表现出抑制作用。