Total synthesis and anticancer activity of highly potent novel glycolipid derivatives

被引：15

作者：

Jung, Mankil ^{[1
]}

Lee, Yongnam ^{[1
]}

Moon, Hyung-In ^{[2
,3
]}

Jung, Youngae ^{[1
]}

Jung, Haein ^{[1
]}

Oh, Miyeon ^{[1
]}

机构：

[1] Yonsei Univ, Dept Chem, Seoul 120749, South Korea

[2] Wonkwang Univ, Dept Neurosci, Kyunggido 435040, South Korea

[3] Wonkwang Univ, Inam Neurosci Res Ctr, Sanbon Med Ctr, Kyunggido 435040, South Korea

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 08期

关键词：

Glycolipid; Total synthesis; Glycosylation; Anticancer activity; Doxorubicin; ANTI-TUMOR; ESTERIFICATION; GLYCOSYLATION; CATALYSTS; LIGANDS; ACIDS; ASSAY;

D O I：

10.1016/j.ejmech.2009.03.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The total synthesis and anticancer activity of several novel derivatives based on a dauer effect-inducing glycolipid are presented. A versatile and convergent synthesis was accomplished through stereospecific a-glycosylation, which produced di- and tri-rhamnoside daumone derivatives. Most of the synthetic derivatives possessed potent anticancer activity against human cancer cell lines. Daumone and deoxyrhammose trisaccharides with amide side chains had the most potent anticancer activity among all other known glycolipids, with an effective concentration of 20 nM, which is comparable to that of doxorubicin. Conversely, acyclic and macrocyclic daumone derivatives had drastically decreased anticancer activity. Due to the high lipophilic nature of the novel glycolipid derivatives, we propose that the observed anticancer activity is due to their potential to inhibit cell differentiation and proliferation via interaction with the membranes of cancer cells. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：3120 / 3129

页数：10