College of Public Health, Anhui University of Science and Technology, Hefei 230000, China.
College of Medicine, Anhui University of Science and Technology, Huainan 232001, China.
Molecules. 2023 Sep 25;28(19):6796. doi: 10.3390/molecules28196796.
Curcumin possesses a wide spectrum of liver cancer inhibition effects, yet it has chemical instability and poor metabolic properties as a drug candidate. To alleviate these problems, a series of new mono-carbonyl curcumin derivatives were designed, synthesized, and evaluated by in vitro and in vivo studies. Compound was found to be the most potent derivative (IC = 15.39 μM) compared to curcumin (IC = 40.56 μM) by anti-proliferation assay. Subsequently, molecular docking, wound healing, transwell, JC-1 staining, and Western blotting experiments were performed, and it was found that compound could suppress cell migration and induce cell apoptosis by inhibiting the phosphorylation of AKT and affecting the expression of apoptosis-related proteins. Moreover, the HepG2 cell xenograft model and H&E staining results confirmed that compound was more effective than curcumin in inhibiting tumor growth. Hence, is a promising leading compound with the potential to be developed as a chemotherapy agent for hepatocellular carcinoma.
姜黄素具有广泛的肝癌抑制作用，但作为候选药物，它具有化学不稳定性和较差的代谢性质。为了缓解这些问题，设计、合成了一系列新的单羰基姜黄素衍生物，并通过体外和体内研究进行了评估。通过抗增殖测定发现，与姜黄素（IC = 40.56 μM）相比，化合物 （IC = 15.39 μM）是最有效的衍生物。随后进行了分子对接、划痕愈合、Transwell、JC-1 染色和 Western blot 实验，结果发现化合物 可以通过抑制 AKT 的磷酸化和影响凋亡相关蛋白的表达来抑制细胞迁移并诱导细胞凋亡。此外，HepG2 细胞异种移植模型和 H&E 染色结果证实，化合物 抑制肿瘤生长的效果优于姜黄素。因此， 是一种很有前途的先导化合物，有可能被开发为治疗肝癌的化疗药物。
