Starting from benzyl 30-oxobetulinate and 30-oxobetulin diacetate, substituted dienes were synthesized and subjected to Diels-Alder reaction, yielding a variety of triterpenoid phthalates, phthalimides, and related derivatives. A total of 55 new compounds were prepared and tested for in vitro cytotoxic activity against eight cancer cell lines and two non-cancerous cell lines. Four compounds with IC50 values of 5 μM or lower were selected for further investigation. These compounds induced apoptosis in CCRF-CEM cells in a concentration-dependent manner, accompanied by mitochondrial depolarization and altered expression of key proteins involved in mitochondrial apoptosis. The compounds also disrupted DNA replication and transcriptional activity. Modulation of key proliferation pathways, including PI3K/Akt and STAT3, further supported the antiproliferative potential of these derivatives. Considering their high cytotoxicity and antiproliferative activity in CCRF-CEM cells, compounds 19, 26, 28, and 30 have been identified as promising candidates for further development.

中文翻译：

---

三萜类邻苯二甲酰亚胺作为靶向线粒体细胞凋亡的选择性抗癌剂


以 30-氧代枸樣酸苄酯和 30-氧代枸樣酸二乙酸苄酯为原料，合成取代的二烯烃，并进行 Diels-Alder 反应，得到多种三萜类邻苯二甲酸酯、邻苯二甲酰亚胺和相关衍生物。共制备了 55 种新化合物，并测试了对 8 种癌细胞系和 2 种非癌细胞系的体外细胞毒活性。选择 4 种 IC50 值为 5 μM 或更低的化合物进行进一步研究。这些化合物以浓度依赖性方式诱导 CCRF-CEM 细胞凋亡，伴随着线粒体去极化和参与线粒体细胞凋亡的关键蛋白表达的改变。这些化合物还破坏了 DNA 复制和转录活性。关键增殖途径（包括 PI3K/Akt 和 STAT3）的调节进一步支持了这些衍生物的抗增殖潜力。考虑到它们在 CCRF-CEM 细胞中的高细胞毒性和抗增殖活性，化合物 19、26、28 和 30 已被确定为进一步开发的有希望的候选者。