Synthesis of cholestane glycosides bearing OSW-1 disaccharide or its 1→4-linked analogue and their antitumor activities

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 18; pp. 5439 - 5442
• Main Authors: Zheng, Dan, Zhou, Liang, Guan, Yuyao, Chen, Xiaozhuo, Zhou, Wanqi, Chen, Xiaoguang, Lei, Pingsheng
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.09.2010; Elsevier
• Subjects: 1→4-Linked disaccharide analogue; Antineoplastic Agents; Antineoplastic Agents, Phytogenic - chemical synthesis; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor activity; Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; Cholestane glycosides; Cholestanes - chemical synthesis; Cholestanes - chemistry; Cholestanes - pharmacology; Cholestenones - chemical synthesis; Cholestenones - chemistry; Cholestenones - pharmacology; Cytotoxicity; Cytotoxins - chemical synthesis; Cytotoxins - chemistry; Cytotoxins - pharmacology; Drug Screening Assays, Antitumor; General aspects; Glycosides - chemical synthesis; Glycosides - chemistry; Glycosides - pharmacology; Humans; Medical sciences; Models, Molecular; Neoplasms - drug therapy; Ornithogalum - chemistry; OSW-1 analogue; Pharmacology. Drug treatments; Saponins - chemical synthesis; Saponins - chemistry; Saponins - pharmacology; Structure-Activity Relationship; Synthesis; 1→4-Linked disaccharide analogue; Cytotoxicity; Synthesis; Cholestane glycosides; OSW-1 analogue; Antineoplastic agent; Steroid; Liver; Lung; Ketol; Disaccharide; Saponin; Ovary; Glycoside; Colon; Secondary alcohol; Chemical synthesis; Tumor cell; Human; Stomach; In vitro; Biological activity; Primary alcohol; Cell line; Cholestane derivatives
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.07.085

Three cholestane glycosides bearing the OSW-1 disaccharide or its 1→4-linked analogue were synthesized, and their cytotoxic activities were determined. Compound 1 showed potent cytotoxicity against five types of human tumor cells, with IC 50 ranging between 1.3 and 73 nM. For further structure–activity relationship (SAR) research of OSW saponins, a cholestane glycoside, namely 3β, 16β, 26-trihydroxycholest-5-en-22-one 16- O-(2- O-4-methoxybenzoyl-β- d-xylopyranosyl)-(1→3)-2- O-acetyl-α- l-arabinopyranoside ( 1) together with two 1→4-linked disaccharide analogues ( 2 and 3) were synthesized. Their cytotoxic activities were evaluated by the standard MTT assay. Compound 1 showed potent cytotoxicity against five types of human tumor cells, with IC 50 ranging between 1.3 and 73 nM.