姜黄素是从姜科和天南星科根茎中提取的，因其抗炎、抗菌、抗氧化和抗癌特性而在临床上使用。它的安全性和潜力使其成为设计增强型衍生品的有前景的基础。现在的重点是优化姜黄素并合成更有效的 1,4-pentadien-3-ones，它们具有抗癌活性。三阴性乳腺癌（TNBC）是一种具有高转移潜力的侵袭性和侵袭性乳腺癌，因此迫切需要创新治疗方法。化疗耐药、复发和 TNBC 异质性带来的挑战强调了新治疗方法的必要性。我们的策略涉及将喹喔啉环整合到1,4-戊二烯-3-酮中，然后进行后续修饰。在这项研究中，N17 展示了诱导细胞死亡并有效抑制乳腺癌细胞增殖的能力。这些观察到的抗癌作用归因于 p-AKT (S473) 的抑制，p-AKT (S473) 是乳腺癌细胞中与细胞凋亡和上皮间质转化过程调节有关的关键调节因子。此外，我们的研究表明，N17 通过特异性靶向 CSNK1G3 蛋白来实现对 p-AKT(S473) 的抑制作用。值得注意的是，N17 不仅阻碍 EMT 过程，还通过 CSNK1G3/AKT 信号轴触发细胞凋亡。这些发现提供了 CSNK1G3 作为 TNBC 中抗癌调节剂的关键作用，确立了 N17 作为一种药物干预手段，在治疗癌症转移方面具有巨大前景。版权所有 © 2024。由 Elsevier Inc. 出版。

Curcumin, extracted from Zingiberaceae and Araceae rhizomes, is clinically used for its anti-inflammatory, antibacterial, antioxidant, and anti-cancer properties. Its safety and potential make it a promising base for designing enhanced derivatives. The focus now is on optimizing curcumin and synthesizing more potent 1,4-pentadien-3-ones, which have anti-cancer activities. In the realm of triple-negative breast cancer (TNBC), an aggressive and invasive form with high metastatic potential, the need for innovative treatments is acute. The challenges posed by chemotherapy resistance, recurrence, and TNBC's heterogeneity have emphasized the necessity for novel therapeutic approaches. Our strategy involved the integration of a quinoxaline ring into 1,4-pentadien-3-one, followed by subsequent modifications. In this study, N17 demonstrated the ability to induce cell death and effectively suppress cell proliferation in breast cancer cells. These observed anti-cancer effects were attributed to the inhibition of p-AKT(S473), a key regulator implicated in both cell apoptosis and the modulation of epithelial-mesenchymal transition process in breast cancer cells. Furthermore, our investigation indicated N17 achieves its inhibitory effects on p-AKT(S473) by specifically targeting the CSNK1G3 protein. Remarkably, N17 not only impedes the EMT process but also triggers apoptosis through the CSNK1G3/AKT signaling axis. These findings provide the critical role of CSNK1G3 as an anti-cancer regulator in TNBC, establishing N17 as a pharmacological intervention with immense promise for treating cancer metastasis.Copyright © 2024. Published by Elsevier Inc.