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.

心脏苷显示出显着的抗癌作用，洋地黄毒苷C ₃位的糖基取代对其生物活性至关重要。为了研究强心苷的朝向癌症结构-活性关系（SAR）和探索更有效的抗癌剂，一系列的C ₃ - ö -neoglycosides和C ₃ -MeO Ñ -neoglycosides洋地黄毒苷的由合成的Koenigs-克诺尔和新糖基化方法。此外，地高辛通过高碘酸钠（NaIO ₄）氧化和6-氨基己酸水解，从地高辛制备了洋地黄毒苷双指氧苷和单指氧苷。SAR分析表明C ₃ - O洋地黄毒苷的β-新糖苷比C ₃ -MeO N-新糖苷显示出更强的细胞毒性和对肿瘤细胞Nur77表达的诱导。另外，3 β - ö -glycosides显示比3更强的抗癌作用α - Ö -glycosides。其中，3 β - ø - （β -升-fucopyranosyl）-digoxigenin（3I）显示出对Nur77表达和转从细胞核至细胞质的诱导最高活性，导致癌细胞凋亡。