Synthesis, conformational analysis and SAR research of OSW-1 analogues

被引：8

作者：

Liu, Chao ^{[1
]}

Wang, A-Peng ^{[1
]}

Jin, Longlong ^{[1
]}

Guo, Yanshen ^{[1
]}

Li, Yan ^{[2
]}

Zhao, Zhehui ^{[1
]}

Lei, Pingsheng ^{[1
]}

机构：

[1] Chinese Acad Med Sci, State Key Lab Bioact Subst & Funct Nat Med, Beijing Key Lab Active Subst Discovery & Drug Abi, Dept Med Chem,Inst Mat Med,Peking Union Med Coll, Beijing 100050, Peoples R China

[2] Chinese Acad Med Sci, Peking Union Med Coll, Inst Mat Med, Dept Pharmacol, Beijing 100050, Peoples R China

来源：

TETRAHEDRON | 2016年 / 72卷 / 27-28期

关键词：

OSW-1; analogues; Synthesis; Conformation analysis; Molecule simulation; Antitumor activity; POTENT ANTITUMOR SAPONIN; CHOLESTANE GLYCOSIDES; OXYSTEROL-BINDING; DISACCHARIDE; BEARING; BULBS; CELLS;

D O I：

10.1016/j.tet.2016.05.049

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A series of novel OSW-1 analogues were synthesized by coupling disaccharides (2-O-4-methoxylbenzoyl-beta-D-xylopyranosyl-(1 -> 3)-2-O-acetyl-alpha-L-arabinopyranosyl) or (2-O-4-(E)-cinnamoyl-beta-D-xylopyranosyl-(1 -> 3)-2-O-acetyl-alpha-L-arabinopyranosyl) and their 1 -> 4 linked analogues [(2-O-4-methoxylbenzoyl-beta-D-xylopyranosyl-(1 -> 4)-2-O-acetyl-alpha-L-arabinopyranosyl) or (2-O-4-(E)-cinnamoyl-beta-D-xylopyranosyl-(1 -> 4)-2-O-acetyl-alpha-L-arabinopyranosyl)] with three different steroidal sapogenins at 16 beta-hydroxy. Their conformation was analyzed with NMR spectroscopy and molecule simulation. The arabinose moiety of 1-3 linked analogues was in chair conformation and 1-4 linked analogues was in boat conformation. 1-3 linked analogues exhibited potent anti-proliferation activity against a panel of human tumor cells at nanomolar concentration level, while 1-4 linked analogues did not show antitumor activity. This work should provide an evidence that the conformation plays an important role in the antitumor activity. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：4091 / 4102

页数：12

共 29 条

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