School of Pharmacy, Bengbu Medical College, Bengbu, Anhui, China.
Anhui Province Biochemical Pharmaceutical Engineering Technology Research Center, Bengbu, Anhui, China.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2244694. doi: 10.1080/14756366.2023.2244694.
In this study, 21 new honokiol derivatives were synthesised, and their anti-cancer properties were investigated. Among these, compound exhibited the most potent cytotoxic activity against human nasopharyngeal carcinoma CNE-2Z cells, human gastric cancer SGC7901 cells, human breast cancer MCF-7 cells, and mouse leydig testicular cancer I-10 lines with IC values of 6.04, 7.17, 6.83, and 5.30 μM, respectively. Compared to the parental compound, displayed up to 5.18-fold enhancement of the cytotoxic effect on CNE-2Z cells. We further demonstrated that inhibited cell growth, suppressed migration and invasion, and induced apoptosis of CNE-2Z cells by down-regulating HIF-1α, MMP-2, MMP-9, Bcl-2, Akt and up-regulating Bax protein levels. Transfection of CNE-2Z cells with HIF-1α siRNA reduced cell migration and invasion. In addition, experiments confirmed that inhibited tumour growth in CNE-2Z cell-xenografted nude mice with low toxicity. Thus, our data suggested that was a potent and safe lead compound for nasopharyngeal carcinoma therapy.
在这项研究中，合成了 21 种新的厚朴酚衍生物，并研究了它们的抗癌特性。在这些化合物中，化合物 对人鼻咽癌细胞 CNE-2Z、人胃癌 SGC7901 细胞、人乳腺癌 MCF-7 细胞和小鼠莱迪希睾丸癌细胞 I-10 的细胞毒性活性最强，IC 值分别为 6.04、7.17、6.83 和 5.30μM。与母体化合物相比，化合物 对 CNE-2Z 细胞的细胞毒性作用增强了 5.18 倍。我们进一步证明，化合物 通过下调 HIF-1α、MMP-2、MMP-9、Bcl-2、Akt 并上调 Bax 蛋白水平，抑制 CNE-2Z 细胞的生长、迁移和侵袭，并诱导其凋亡。用 HIF-1α siRNA 转染 CNE-2Z 细胞可降低细胞迁移和侵袭。此外， 实验证实化合物 对荷瘤裸鼠的肿瘤生长有抑制作用，且毒性低。因此，我们的数据表明，化合物 是一种治疗鼻咽癌的有效且安全的先导化合物。
