设计合成了萘酰亚胺的4种新的多胺衍生物并进行了体外抗肿瘤活性测试.结果表明,这些萘酰亚胺衍生物能够嵌入DNA碱基对中,并且比氨萘非特对肿瘤细胞具有更高的毒性和更好的选择性,其中化合物3b对4种肿瘤细胞的抑制IC50值分别为7.80、5.08、9.78和9.27 μmol/L;高内涵活细胞成像系统结果显示,这些化合物可能是通过线粒体通路而导致的细胞凋亡.
参考文献
| [1] | O'Brien P J,Irwin W,Diaz D,et al.High Concordance of Drug-induced Human Hepatotoxicity with in vitro Cytotoxicity Measured in a Novel Cell-based Model Using High Content Screening[J].Arch Toxicol,2006,80(9):580-604. |
| [2] | Bra(n)a M F,Ramos A.Naphathalimides as Anticancer Agents:Synthesis and Biological Activity[J].Curr Med Chem,2001,1(3):237-255. |
| [3] | Lv M,Xu H.Overview of Naphthalimide Analogs as Anticancer Agents[J].Curr Med Chem,2009,16(36):4797-4813. |
| [4] | Van Quaquebeke E,Mahieu T,Dumont P,et al.2,2,2-Trichloro-N-(｛2-[2-(dimethyl-amino) ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl ｝ carbamoyl) acetamide (UNBS3157),a Novel Nonhematotoxic Naphthalimide Derivative with Potent Antitumor Activity[J].J Med Chem,2007,50(17):4122-4134. |
| [5] | Tumiatti V,Milelli A,Minarini A,et al.Design,Synthesis,and Biological Evaluation of Substituted Naphthalene Imides and Diimides as Anticancer Agent[J].J Med Chem,2009,52(23):7873-7877. |
| [6] | Barron G A,Bermano G,Gordon A,et al.Synthesis,Cytotoxicity and DNA-Binding of Novel Bisnaphthalimidopropyl Derivatives in Breast Cancer MDA-MB-231 Cells[J].Eur J Med Chem,2010,45(4):1430-1437. |
| [7] | Li X L,Lin Y J,Wang Q Q,et al.The Novel Anti-tumor Agents of 4-Triazol-1,8-naphthalimides:Synthesis,Cytotoxicity,DNA Intercalation and Photocleavnge[J].Eur J Med Chem,2011,46(4):1274-1279. |
| [8] | Tian Z Y,Xie S Q,Mei Z H,et al.Conjugation of Substituted Naphthalimides to Polyamines as Cytotoxic Agents Targeting the Akt/mTOR Signal Pathway[J].Org BiomolChem,2009,7(22):4651-4660. |
| [9] | MEI Zihou,TIAN Zhiyong,MA Hongxia,et al.Synthesis andin vitro Cytotoxicity of Naphthalimide Polyamine Conjugates as Antitumor Agents[J].Acta Pharm Sin,2009,44(7):754-757(in Chinese).梅子厚,田智勇,马红霞,等.萘酰亚胺-多胺缀合物的合成及体外抗癌活性[J].药学学报,2009,44(7):754-757. |
| [10] | Xie S Q,Li Q,Zhang Y H,et al.NPC-16,a Novel Naphthalimide-polyamine Conjugate,Induced Apoptosis and Autophagy in Human Hepatoma HepG2 Cells and Bel-7402 Cells[J].Apoptosis,2011,16(1):27-34. |
| [11] | MIAO Jiuwang.Antitumor Effects of XHH,a Novel Nitrogen Mustard Derivative,and Its Mechanisms[D].Kaifeng:Henan University,2010(in Chinese).苗久旺.新型氮芥衍生物XHH抗肿瘤作用及机制研究[D].开封:河南大学,2010. |
| [12] | Janne J,Alhonen L,Leinonen P.Polyamines:from Molecular Biology to Clinical Applications[J].Ann Med,1991,23(3):241-259. |
| [13] | Mosmann T.Rapid Colorimetric Assay for Cellular Growth and Survival:Application to Proliferation and Cytotoxicity Assays[J].J Immunol Methods,1983,65(1/2):55-63. |
| [14] | Wang C,Delcros J G,Biggerstaff J,et al.Synthesis and Biological Evaluation of Polyamine-anthracene Conjugates[J].J Med Chem,2003,46(13):2672-2682. |
| [15] | Wang C,Delcros J G,Cannon L,et al.Defining the Molecular Requirements for the Selective Delivery of Polyamine Conjugates into Cells Containing Active Polyamine Transporters[J].J Med Chem,2003,46(13):5129-5138. |
| [16] | ZHANG Li,DU Guanhua.High Content Drug Screening and Its Application[J].Acta Pharm Sin,2005,40 (6):486-490(in Chinese).张莉,杜冠华.高内涵药物筛选方法的研究及应用[J].药学学报,2005,40(6):486-490. |
| [17] | Long E C,Barton J K.On Demonstrating DNA Intercalation[J].Acc Chem Res,1990,23(9):271-273. |
| [18] | Sahoo D,Bhattacharya P,Chakravorti S.Quest for Mode of Binding of 2-(4-(Dimethylamino) styryl)-1-methylpyridinium Iodide with Calf Thymus DNA[J].J Phys Chem B,2010,114(5):2044-2050. |
| [19] | Wang K,Wang Y,Yan X,et al.DNA Binding and Anticancer Activity of Naphthalimides with 4-Hydroxyl-alkylamine Side Chains at Different Lengths[J].Bioorg Med Chem Lett,2012,22(2):937-941. |
上一张
下一张
上一张
下一张
计量
- 下载量()
- 访问量()
文章评分
- 您的评分：
-
10%
-
20%
-
30%
-
40%
-
50%