School of Medicine, Huanghe Science and Technology College, Zhengzhou 450063, China.
National Health Commission Key Laboratory of Birth Defect Prevention, Henan Institute of Reproductive Health Science and Technology, Zhengzhou 450002, China.
Molecules. 2022 Jul 25;27(15):4738. doi: 10.3390/molecules27154738.
Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin-nucleoside conjugates - were designed and synthesized for potency improvement. Compounds , , and showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin () evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon's antitumor activity based on our present study.
别桦脂醇结构上与白桦脂酸类似，能够诱导癌细胞凋亡，同时具有较低的毒性。然而，它们对几种肿瘤细胞系的增殖抑制作用都较弱。因此，我们设计并合成了一系列新的别桦脂醇/别桦脂烷核苷缀合物，以提高其效力。与齐多夫定、顺铂和奥沙利铂相比，化合物 、 、 和 对 6 种测试细胞系的增殖具有良好的抑制活性，根据其抗肿瘤活性结果。其中，化合物 对 SMMC-7721、HepG2、MNK-45、SW620 和 A549 人癌细胞系的增殖抑制活性明显强于顺铂和奥沙利铂。在作用机制的初步研究中，化合物 在 SMMC 细胞中诱导细胞凋亡和自噬，通过调节 Bax、Bcl-2 和 LC3 的蛋白表达水平，导致增殖抑制和 G0/G1 细胞周期停滞。因此，基于我们目前的研究，核苷取代是提高别桦脂醇/别桦脂烷抗肿瘤活性的可行策略。
