研究动态
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作为抗癌活性的有效 Bax 激动剂的芒柄花素衍生物的合成、分子对接研究。

Synthesis, molecular docking studies of formononetin derivatives as potent Bax agonists for anticancer activity.

发表日期:2023 Nov 03
作者: Wei-Dong Jia, Xue Bai, Qian-Qian Ma, Ming Bian, Chun-Mei Bai, Di Li, Li-Fei Li, Cheng-Xi Wei, Li-Jun Yu
来源: Cellular & Molecular Immunology

摘要:

Formononetin 作为 Bax 激动剂具有抗癌作用。为了鉴定新型 Bax 激动剂,合成了 18 种新的结构修饰芒柄花素衍生物,并在 A549 和 Beas-2b 细胞系中评估了它们的抗癌活性。结果表明,7a对A549细胞系具有最强的抑制作用,IC50值为0.87μM,对Beas-2b细胞无明显毒性。这些结果表明,7a 的功效分别是芒柄花素和阿霉素的 40 倍和 6.94 倍。此外,Western blot和免疫荧光实验表明,7a下调Bcl-2蛋白表达,上调Bax表达,促进A549凋亡,所得结果也表明7a有潜力开发成可应用的先导化合物。在肺癌的预防和治疗中。
Formononetin as a Bax agonist exhibits anticancer effects. To identify novel Bax agonist, 18 new structurally modified formononetin derivatives were synthesised and their anticancer activities were evaluated in the A549 and Beas-2b cell lines. The results indicated that 7a elicited the most potent inhibitory effect against the A549 cell line, with an IC50 value of 0.87 μM, and no obvious toxicity to Beas-2b cells. These results indicated that 7a was 40-fold and 6.94-fold more efficacious than Formononetin and Doxorubicin, respectively. Additionally, western blot and immunofluorescence assays demonstrated that 7a downregulated the protein expression of Bcl-2 and upregulated the expressions of Bax to promote A549 apoptosis, the obtained results also suggested that 7a had the potential to be developed into a lead compound that can be applied in the prevention and treatment of lung cancer.