设计合成了4种N,N-二(8-黄酮甲基)香叶胺类化合物,所有目标化合物的结构均经~1H NMR、MS和元素分析测试技术确证.采用MTT法考察了目标化合物对K562(白血病细胞)和SMMC7721(肝癌细胞)2种肿瘤细胞的体外抑制活性.结果表明,所测化合物对2种肿瘤细胞均有体外抑制活性,其中N,N-二(3',4'-二甲氧基-8-黄酮甲基)香叶胺(1c)的活性最好,IC_(50)值分别为5.78和3.85 μmol/L,N,N-二(4'-氟-8-黄酮甲基)香叶胺(1a)和化合物1c对K562(白血病细胞)的体外抑制活性明显优于商品药物美法仑(Melphalan).以溴化乙锭(EB)为荧光探针观测到化合物1c与鲱魚精DNA有较强的相互作用.
Four N,N-bis(8-flavonmethyl)geranylamine derivatives were designed and synthesized. The structures of the synthesized compounds were determined from the results of ~1H NMR, MS and elemental analysis. The prelimilary cytotoxicity was evaluated on K562 and SMMC7721 cell lines by MTT assay. The results demonstrate that all the compounds possess antitumor actitity and compound 1c is the best among them with an IC_(50) value of 5.78 μmol/L or 3.85 μmol/L against K562 or SMMC7721 cell lines, respectively. The in vitro antitumor activities of compounds 1a and 1c against K562 were better than that of the commercial drug Melphalan. The interaction of compound 1c with herring sperm DNA was explored with ethidium bromide(EB) as a fluorescence probe. The result of the study on fluorescence quenching by DNA-EB confirms the strong interaction of compound 1c with Herring Sperm DNA.
参考文献
| [1] | Morikawa T,Xu F M,Matsuda H.Chem Pharm Bull[J],2006,54(11):1 530 |
| [2] | Williams C A,Grayer R J.Nat Prod Rep[J],2004,21:539 |
| [3] | Murthi K K,Dubay M,MccLure C,Brizuela L,Boisclair M D,Worland P J,Mansuri M M,Pal K.Bioorg Med Chem Lett[J],2000,10:1 037 |
| [4] | Carnesecchi S,Langley K,Exinger F,Gosse F,Raul F.J Pharmacol Exp Ther[J],2002,301(2):625 |
| [5] | Chi Y S,Jong H G,Son K H,Chang H W,Kang S S,Kim H P.Biochem Pharmacol[J],2001,62:1 185 |
| [6] | Epifano F,Genovese S,Menghini L,Curini M.Phytochemisrty[J],2007,68:939 |
| [7] | Daskiewicz J B,Depeint F,Viornery L,Bayet C,Comtesarrazin G,Comte G,Gee J M,Johnson I T,Ndjoko K,Hostettmann K,Barron D.J Med Chem[J],2005,48(8):2 790 |
| [8] | ZHAO Jin(赵瑾),LIU Yang(刘洋),ZHENG Mei-Hua(郑梅花),XIE Song-Qiang(谢松强),WANG Chao-Jie(王超杰).Chinese J Org Chem(有机化学)[J],2008,28(1):84 |
| [9] | ZHAO Jin(赵瑾),LIU Lei(刘蕾),SONG Jin-Yong(宋金勇),WANG Chao-Jie(王超杰).Chinese J Org Chem(有机化学)[J],2004,24(12):1 601 |
| [10] | ZHAO Jin(赵瑾),SONG Jin-Yong(宋金勇),WANG Chao-Jie(王超杰),LIU Lei(刘蕾),SUN Xin-Qi(孙心奇).Chinese J Appl Chem(应用化学)[J],2003,20:95 |
| [11] | SUN Zhi-Zhong(孙志忠),HOU Yan-Jun(侯艳君),CHU Wen-Yi(初文毅),LI Jing-Fang(李敬芳).J Nat Sci Heilongjiang Univ(黑龙江大学自然科学学报)[J],2004,21(2):122 |
| [12] | Gardner R A,Kinkade R,Wang C J,Phanstiel IV O.J Org Chem[J],2004,66(10):3 530 |
- 下载量()
- 访问量()
- 您的评分：
-
10%
-
20%
-
30%
-
40%
-
50%