新型bakuchiol衍生物的合成及抗乳腺癌评价。

IF 2.2 4区 医学 Q3 CHEMISTRY, MEDICINAL
Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-12-01 Epub Date: 2025-08-06 DOI:10.1016/j.bmcl.2025.130361
Hong-Mei Li, Jing Zhu, Ke Zhong, Jie Chen, Long Zhao, Zhen-Hai Zhang, Cheng-Zhu Wu
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引用次数: 0

摘要

在本研究中,我们半合成了19种新的白草酚衍生物,并评价了它们的抗乳腺癌性质。其中化合物19对MDA-MB-231细胞具有显著的细胞毒活性,IC50值为4.13 μM。值得注意的是,化合物19对正常小鼠肝细胞(Aml-12)的细胞毒性明显较低,IC50值为31.60 μM。我们的研究结果表明,化合物19通过增加Bax和Cyt - C的水平,减少Bcl-2,并启动caspase-3切割,从而引发MDA-MB-231细胞的凋亡。通过下调MMP-2和MMP-9表达,上调E-cadherin蛋白水平,抑制MDA-MB-231细胞的侵袭和迁移。我们进一步证明,化合物19能显著抑制MDA-MB-231细胞移植裸鼠的肿瘤生长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and anti-breast cancer evaluation of new bakuchiol derivatives.

In this study, we semi-synthesized nineteen new derivatives of bakuchiol and evaluated their anti-breast cancer properties. Among them, compound 19 stood out as the most effective demonstrating significant cytotoxic activity against MDA-MB-231 cells, with IC50 values of 4.13 μM. Notably, the cytotoxicity of compound 19 towards normal mouse hepatocytes (Aml-12) cells was considerably lower, with IC50 values of 31.60 μM. Our findings indicated that compound 19 triggered apoptosis in MDA-MB-231 cells by increasing the levels of Bax and Cyt C, reducing Bcl-2, and initiating caspase-3 cleavage. It also suppressed the invasion and migration of MDA-MB-231 cells by down-regulating MMP-2 and MMP-9 expression and up-regulating E-cadherin protein levels. We further demonstrated that compound 19 significantly suppressed tumor growth in nude mice xenografted with MDA-MB-231 cells.

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来源期刊
CiteScore
5.70
自引率
3.70%
发文量
463
审稿时长
27 days
期刊介绍: Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
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