Institute of Molecular Toxicology and Pharmacology, Wenzhou Medical University, 1210 University Town, Wenzhou 325035, Zhejiang, China.
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou 325035, Zhejiang, China.
J Agric Food Chem. 2024 Apr 3;72(13):7244-7255. doi: 10.1021/acs.jafc.4c00882. Epub 2024 Mar 22.
The instability of curcumin's structure and the toxic side effects of piperlongumine have limited their potential applications in cancer treatment. To overcome these challenges, we designed and synthesized a novel curcumin-piperlongumine hybrid molecule, 3-[()-4-hydroxy-3-methoxybenzylidene]-1-[()-3-(3,4,5-trimethoxyphenyl)acryloyl]piperidin-2-one (CP), using a molecular hybridization strategy. CP exhibited enhanced structural stability and safety compared with its parent compounds. Through in vitro and in vivo biological activity screenings, CP effectively inhibited cell proliferation, caused cell cycle arrest in the G2/M phase, and induced apoptosis. Mechanistically, CP-induced apoptosis was partially mediated by cell cycle arrest. Furthermore, we discovered that CP induces cell cycle arrest and apoptosis through the regulation of JNK signaling. These findings highlight the potential of CP as a promising therapeutic agent for lung cancer treatment.
姜黄素结构的不稳定性和胡椒碱的毒副作用限制了它们在癌症治疗中的潜在应用。为了克服这些挑战，我们设计并合成了一种新型的姜黄素-胡椒碱杂合分子，3-[()-4-羟基-3-甲氧基苄叉基]-1-[()-3-(3,4,5-三甲氧基苯基)丙烯酰基]哌啶-2-酮（CP），采用分子杂交策略。CP 与母体化合物相比，表现出增强的结构稳定性和安全性。通过体外和体内生物活性筛选，CP 有效抑制细胞增殖，导致 G2/M 期细胞周期停滞，并诱导细胞凋亡。机制上，CP 诱导的细胞凋亡部分是通过细胞周期阻滞介导的。此外，我们发现 CP 通过调节 JNK 信号诱导细胞周期阻滞和细胞凋亡。这些发现强调了 CP 作为一种有前途的肺癌治疗药物的潜力。
