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

IF 1.9 3区化学 Q3 CHEMISTRY, APPLIED Natural Product Research Pub Date : 2025-02-01 DOI:10.1080/14786419.2023.2269592

Wei-Dong Jia , Xue Bai , Qian-Qian Ma , Ming Bian , Chun-Mei Bai , Di Li , Li-Fei Li , Cheng-xi Wei , Li-Jun Yu

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Abstract

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.

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作为具有抗癌活性的强效Bax激动剂的甲素衍生物的合成、分子对接研究。

Formononetin作为Bax激动剂具有抗癌作用。为了鉴定新的Bax激动剂，合成了18种新的结构修饰的甲素衍生物，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细胞株的抑制作用最强，IC50值为0.87 μM，对Beas-2b细胞无明显毒性。这些结果表明，7a的疗效分别是Formononetin和Doxorubicin的40倍和6.94倍。此外，western印迹和免疫荧光检测表明，7a下调Bcl-2蛋白表达，上调Bax蛋白表达，促进A549细胞凋亡，这也表明7a具有发展成为可用于预防和治疗癌症的先导化合物的潜力。

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来源期刊

Natural Product Research 化学-医药化学

CiteScore

5.10

自引率

9.10%

发文量

605

审稿时长

2.1 months

期刊介绍： The aim of Natural Product Research is to publish important contributions in the field of natural product chemistry. The journal covers all aspects of research in the chemistry and biochemistry of naturally occurring compounds. The communications include coverage of work on natural substances of land and sea and of plants, microbes and animals. Discussions of structure elucidation, synthesis and experimental biosynthesis of natural products as well as developments of methods in these areas are welcomed in the journal. Finally, research papers in fields on the chemistry-biology boundary, eg. fermentation chemistry, plant tissue culture investigations etc., are accepted into the journal. Natural Product Research issues will be subtitled either ""Part A - Synthesis and Structure"" or ""Part B - Bioactive Natural Products"". for details on this , see the forthcoming articles section. All manuscript submissions are subject to initial appraisal by the Editor, and, if found suitable for further consideration, to peer review by independent, anonymous expert referees. All peer review is single blind and submission is online via ScholarOne Manuscripts.