标题：Synthesis and Biological Evaluation of Curcumin Derivatives with Water-Soluble Groups as Potential Antitumor Agents: An in Vitro Investigation Using Tumor Cell Lines
作者：Ding, Luyang; Ma, Shuli; Lou, Hongxiang; Sun, Longru; Ji, Mei
作者机构：[Ding, Luyang; Ma, Shuli; Lou, Hongxiang; Sun, Longru; Ji, Mei] Shandong Univ, Sch Pharmaceut Sci, Dept Nat Prod Chem, Key Lab Chem Biol MOE, Jinan 25 更多
通讯作者地址：[Sun, LR]Shandong Univ, Sch Pharmaceut Sci, Dept Nat Prod Chem, Key Lab Chem Biol MOE, 44 West Wenhua Rd, Jinan 250012, Peoples R China.
关键词：curcumin; curcumin derivatives; synthesis; antitumor cell line growth; activity; apoptosis
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 mu M against HeLa cells compared with curcumin with an IC50 of 17.67 mu M. 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.