Synthesis and potent antileukemic activities of 10-benzyl-9(10H)-acridinones

被引：45
作者：
Gao, Chunmei [1 ]
Jiang, Yuyang [1 ,2 ]
Tan, Chunyan [1 ]
Zu, Xuyu [1 ]
Liu, Huachen [1 ]
Cao, Derong [3 ]
机构：
[1] Tsinghua Univ, Grad Sch Shenzhen, Key Lab Chem Biol, Shenzhen 518055, Peoples R China
[2] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China
[3] S China Univ Technol, Coll Chem, Guangzhou 510640, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 18期
基金：
中国博士后科学基金;
关键词：
acridinone derivatives; antileukemia agent; antiproliferative activity; apoptosis;
D O I：
10.1016/j.bmc.2008.07.086
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A novel series of 10-benzyl-9(10H)-acridinones and 1-benzyl-4-piperidones were synthesized and tested for their in vitro antitumor activities against CCRF-CEM cells. Assay-based antiproliferative activity study using CCRF-CEM cell lines revealed that the acridone group and the substitution pattern on the benzene unit had significant effect on cytotoxicity of this series of compounds, among which 10-(3,5-dimethoxy) benzyl-9(10H)-acridinone (3b) was found to be the most active compound with IC(50) at about 0.7 mu M. Compound 3b was also found to have antiproliferative activity against two other human leukemic cell lines K562 and HL60 using the MTT assay. The antitumor effect of 3b is believed to be due to the induction of apoptosis, which is further confirmed by PI ( Propidium iodide) staining and Annexin V-FITC/PI staining assay using flow cytometry analysis. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码：8670 / 8675
页数：6
相关论文
共 36 条
  • [1] SAR of a series of anti-HSV-1 acridone derivatives, and a rational acridone-based design of a new anti-HSV-1 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine series
    Bernardino, Alice M. R.
    Castro, Helena C.
    Frugulhetti, Lzabel C. P. P.
    Loureiro, Natalia I. V.
    Azevedo, Alexandre R.
    Pinheiro, Luiz C. S.
    Souza, Thiago M. L.
    Giongo, Viveca
    Passamani, Fabiana
    Magalhaes, Uiaran O.
    Albuquerque, Magaly G.
    Cabral, Lucio M.
    Rodrigues, Carlos R.
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (01) : 313 - 321
  • [2] Acridone derivatives: Design, synthesis, and inhibition of breast cancer resistance protein ABCG2
    Boumendjel, Ahcene
    Macalou, Sira
    Ahmed-Belkacem, Abdelhakim
    Blanc, Madeleine
    Di Pietro, Attilio
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (08) : 2892 - 2897
  • [3] In vitro cytotoxicity activity on several cancer cell lines of acridone alkaloids and N-phenylethyl-benzamide derivatives from Swinglea glutinosa (Bl.) Merr.
    Braga, P. A. C.
    Dos Santos, D. A. P.
    da Silva, M. F. G. F.
    Vieira, P. C.
    Fernandes, J. B.
    Houghton, P. J.
    Fang, R.
    [J]. NATURAL PRODUCT RESEARCH, 2007, 21 (01) : 47 - 55
  • [4] A facile synthesis of homotriptycenes from anthranol derivatives
    Cao, DR
    Gao, CM
    Meier, H
    [J]. SYNLETT, 2005, (20) : 3166 - 3168
  • [5] Discovery and structure-activity studies of a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors
    Connolly, CJC
    Hamby, JM
    Schroeder, MC
    Barvian, M
    Lu, GH
    Panek, RL
    Amar, A
    Shen, C
    Kraker, AJ
    Fry, DW
    Klohs, WD
    Doherty, AM
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (18) : 2415 - 2420
  • [6] Deeb D, 2007, ANTICANCER RES, V27, P3035
  • [7] A novel kind of nitrogen heterocycle compound induces apoptosis of human chronic myelogenous leukemia K562 cells
    Ding, Guoyu
    Liu, Feng
    Yang, Ting
    Jiang, Yuyang
    Fu, Hua
    Zhao, Yufen
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (11) : 3766 - 3774
  • [8] Synthesis and antitumor activity of conjugates of muramyldipeptide or normuramyldipeptide with hydroxyacridine/acridone derivatives
    Dzierzbicka, K
    Kolodziejczyk, AM
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (01) : 183 - 189
  • [9] Synthesis and antitumor activity of conjugates of muramyldipeptide, normuramyldipeptide, and desmuramylpeptides with acridine/acridone derivatives
    Dzierzbicka, K
    Kolodziejczyk, AM
    Wysocka-Skrzela, B
    Mysliwski, A
    Sosnowska, D
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (22) : 3606 - 3615
  • [10] Survival and apoptosis:: a dysregulated balance in liver cancer
    Fabregat, Isabel
    Roncero, Cesar
    Fernandez, Margarita
    [J]. LIVER INTERNATIONAL, 2007, 27 (02) : 155 - 162
1234