Synthesis of C3-Neoglycosides of digoxigenin and their anticancer activities.
Cardiac glycosides exhibit significant anticancer effects and the glycosyl substitution at C3 position of digoxigenin is pivotal for their biological activity. In order to study the structure-activity relationship (SAR) of cardiac glycosides toward cancers and explore more potent anticancer agents, a series of C3-O-neoglycosides and C3-MeON-neoglycosides of digoxigenin were synthesized by the Koenigs-Knorr and neoglycosylation method, respectively. In addition, digoxigenin bisdigitoxoside and monodigitoxoside were prepared from digoxin by sodium periodate (NaIO4) oxidation and 6-aminocaproic acid hydrolysis. The SAR analysis revealed that C3-O-neoglycosides of digoxigenin exhibited stronger cytotoxicity and induction of Nur77 expression of tumor cells than C3-MeON-neoglycosides. Also, 3β-O-glycosides exhibited stronger anticancer effects than 3α-O-glycosides. Among them, 3β-O-(β-l-fucopyranosyl)-digoxigenin (3i) showed the highest activity on induction of Nur77 expression and translocation from the nucleus to cytoplasm, leading to cancer cell apoptosis.
['Li|Xiao-San|XS|', 'Ren|Yi-Chang|YC|', 'Bao|Yu-Zhou|YZ|', 'Liu|Jie|J|', 'Zhang|Xiao-Kun|XK|', 'Zhang|You-Wei|YW|', 'Sun|Xue-Long|XL|', 'Yao|Xin-Sheng|XS|', 'Tang|Jin-Shan|JS|']
D000970:Antineoplastic Agents D049109:Cell Proliferation D004076:Digoxigenin D004305:Dose-Response Relationship, Drug D004354:Drug Screening Assays, Antitumor D006027:Glycosides D006801:Humans D015394:Molecular Structure D013329:Structure-Activity Relationship D014407:Tumor Cells, Cultured
Digoxigenin Anticancer Cytotoxicity Apoptosis MeON-Noeglycosylation Nur77 nuclear receptor O-neoglycosylation