Synthesis and Biological Evaluation of Curcumin Derivatives with Water-Soluble Groups as Potential Antitumor Agents: An in Vitro Investigation Using Tumor Cell Lines

Molecules

Luyang Ding²  Shuli Ma²  Hongxiang Lou²  Longru Sun¹  Mei Ji² 

[1]Department of Natural Products Chemistry, Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan 250012, China

关键词: curcumin;    curcumin derivatives;    synthesis;    antitumor cell line growth activity;    apoptosis;   

DOI  :  10.3390/molecules201219772

来源: mdpi

【 摘 要 】

Three series of curcumin derivatives including phosphorylated, etherified, and esterified products of curcumin were synthesized, and their anti-tumor activities were assessed against human breast cancer MCF-7, hepatocellular carcinoma Hep-G2, and human cervical carcinoma HeLa cells. Compared with curcumin, compounds 3, 8, and 9 exhibited stronger antitumor cell line growth activities against HeLa cells. Compound 12 also showed higher antitumor cell line growth activities on MCF-7 cells than curcumin. Among them, 4-((1E,6E)-7-(4-Hydroxy-3-methoxyphenyl)-3,5-dioxohepta-1,6-dienyl)-2-methoxyphenyl dihydrogen phosphate(3) showed the strongest activity with an half maximal inhibitory concentration (IC₅₀) of 6.78 µM against HeLa cells compared with curcumin with an IC₅₀ of 17.67 µM. Stabilities of representatives of the three series were tested in rabbit plasma in vitro, and compounds 3 and 4 slowly released curcumin in plasma. The effect of compound 3 on HeLa cell apoptosis was determined by examining morphological changes by DAPI (4′,6-diamidino-2-phenylindole) staining as well as Annexin V-FITC/ Propidium Iodide (PI) double staining and flow cytometry. The results showed that 3 induced cellular apoptosis in a dose-dependent manner. Together our findings show that 3 merits further investigation as a new potential antitumor drug candidate.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.