Chikusetsusaponin IVa butyl ester (CS-IVa-Be) is a triterpene saponin that acts as a novel IL6R antagonist for inducing breast cancer cell apoptosis. However, the structure–activity relationship for this class of saponins remains unclear. Here, we report a gram-scale synthesis of CS-IVa-Be and the efficient preparation of eight of its analogues. CS-IVa-Be was demonstrated to have significant antitumor activities against MDA-MB-231, HepG2, and A549 cells. When one of the sugar residues at either the 3-OH or 28-COOH position of CS-IVa-Be was cleaved, or the length of the alkyl chain on the d-glucuronic acid residue of CS-IVa-Be was changed, these analogues showed varied inhibitory activities against the cancer cell lines. Notably, the carboxylic acid form of CS-IVa-Be exhibited a stronger antitumor activity against MDA-MB-231 cells. Furthermore, the carboxylic acid form of CS-IVa-Be inhibited MDA-MB-231 cell proliferation in a dose-dependent manner by arresting the cell cycle at the G2/M phase.

Chikusetsusaponin IVa butester (CS-IVa-Be) 是一种三萜皂苷，可作为新型 IL6R 拮抗剂，诱导乳腺癌细胞凋亡。然而，此类皂苷的构效关系仍不清楚。在这里，我们报告了 CS-IVa-Be 的克级合成及其八种类似物的有效制备。 CS-IVa-Be 被证明对 MDA-MB-231、HepG2 和 A549 细胞具有显着的抗肿瘤活性。当CS-IVa-Be的3-OH或28-COOH位置上的糖残基之一被裂解时，或者CS-IVa-Be上的烷基链的长度dCS-IVa-Be的β-葡萄糖醛酸残基发生改变，这些类似物对癌细胞系表现出不同的抑制活性。值得注意的是，CS-IVa-Be 的羧酸形式对 MDA-MB-231 细胞表现出更强的抗肿瘤活性。此外，CS-IVa-Be 的羧酸形式通过将细胞周期阻滞在 G2/M 期，以剂量依赖性方式抑制 MDA-MB-231 细胞增殖。