Based on the fact that 25-OCH₃-PPD, a natural ginsengenin isolated from the leaves of Panax ginseng, is a promising lead compound, novel 25-OCH₃-PPD derivatives were synthesized to find more potent anti-tumor agents by a simple and facile synthetic method. These derivatives were classified into three types and screened for their cytotoxic activities against seven human cancer cell lines. Compared with 25-OCH₃-PPD, compounds a5, a7, b5 and b7 exhibited higher anti-tumor activities on all tested cell lines with almost 5-fold to 15-fold increases. In particular, compound a7 showed the greatest cytotoxic activity against α-2 cells (IC₅₀ = 2.4 ± 0.4 μM). The preliminary study on the mechanisms indicated that compound a7 could induce α-2 cell apoptosis. Structure–activity relationships demonstrated that the carbon–carbon double bond at the C-20 position could enhance the antiproliferative activity. In conclusion, the novel derivatives a5, a7, b5 and b7 could be further studied as potential candidates for the treatment of cancer. This research provides a theoretical reference for the exploration of new antiproliferative agents.

中文翻译：

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一锅合成，新型25-OCH ₃ -PPD衍生物的抗肿瘤评价和结构-活性关系

基于从人参叶片中分离出的天然人参皂甙25-OCH ₃ -PPD是有前途的先导化合物，合成了新颖的25-OCH ₃ -PPD衍生物，可通过简单的方法找到更有效的抗肿瘤药简便的合成方法。这些衍生物被分为三种类型，并筛选了它们对七种人类癌细胞系的细胞毒活性。与25-OCH ₃ -PPD相比，化合物a5，a7，b5和b7在所有测试的细胞系中均表现出较高的抗肿瘤活性，几乎增加了5倍至15倍。特别是化合物a7表现出对α-2细胞最大的细胞毒活性（IC ₅₀ = 2.4±0.4μM）。机理初步研究表明，化合物a7可诱导α-2细胞凋亡。结构-活性关系表明，C-20位的碳-碳双键可以增强抗增殖活性。总之，可以进一步研究新的衍生物a5，a7，b5和b7作为治疗癌症的潜在候选药物。该研究为新型抗增殖剂的探索提供了理论参考。