Synthesis and Biological Evaluation of Novel Pyrimido[4,5-b]quinoline-2,4-dione Derivatives as MDM2 Ubiquitin Ligase Inhibitors

被引：4
|
作者：
Dou, Xiaoxue [1 ]
Li, Xin [1 ]
Tao, Liu [1 ]
Hu, Chunqi [1 ]
Zhang, Lei [2 ]
He, Qiaojun [2 ]
Yang, Bo [2 ]
Hu, Yongzhou [1 ]
机构：
[1] Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China
[2] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol & Toxicol, Hangzhou 310058, Zhejiang, Peoples R China
来源：
MEDICINAL CHEMISTRY | 2013年 / 9卷 / 04期
基金：
中国国家自然科学基金;
关键词：
Cytotoxic activity; MDM2 E3 ligase inhibitory activity; p53-MDM2 binding inhibitor; pyrimido[4,5-b]quinoline-2,4-dione;
D O I：
10.2174/1573406411309040012
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of pyrimido[4,5-b]quinoline-2,4-dione derivatives was synthesized and evaluated for their cytotoxic activities in vitro against five human cancer cell lines. Selected compounds were tested for their MDM2 E3 ligase inhibitory activities and p53-MDM2 binding inhibitory activities. Among tested compounds, four sulfur-containing compounds (4-7) displayed enhanced cytotoxic activities and better MDM2 E3 ligase inhibitoty activities in comparison with that of HLI98c. Three compounds (4-6) showed better p53-MDM2 binding inhibitory potency with IC50 values ranging from 1.3 mu M to 9.0 mu M.
引用
收藏
页码：581 / 587
页数：7
相关论文
共 50 条
  • [1] SYNTHESIS OF PYRIMIDO(4,5-B)QUINOLINE DERIVATIVES
    ROBEV, SK
    DOKLADI NA BOLGARSKATA AKADEMIYA NA NAUKITE, 1978, 31 (05): : 551 - 554
  • [2] NEW SYNTHESIS OF PYRIMIDO[4,5-B]QUINOLINE-2,4(1H,3H)-DIONE (5-DEAZAALLOXAZINE) DERIVATIVES
    SENGA, K
    SHIMIZU, K
    NISHIGAKI, S
    YONEDA, F
    HETEROCYCLES, 1977, 6 (9-10) : 1361 - 1364
  • [3] Synthesis of Some Pyrimido[4,5-b]quinoline Derivatives
    Marjani, Ahmad Poursattar
    Khalafy, Jabbar
    Ebrahimlo, Ali Reza Molla
    Prager, Rolf H.
    BULLETIN OF THE KOREAN CHEMICAL SOCIETY, 2011, 32 (07) : 2183 - 2186
  • [4] Synthesis of novel pyrimido[4,5-b]quinoline derivatives as dual EGFR/HER2 inhibitors as anticancer agents
    Ibrahim, Nahla Said M.
    Kadry, Hanan H.
    Zaher, Ashraf F.
    Mohamed, Khaled O.
    ARCHIV DER PHARMAZIE, 2024, 357 (03)
  • [5] NOVEL SYNTHESIS OF 2,4-DIPHENYLPYRIMIDO [4,5-B] QUINOLINE
    RANADE, AC
    MALI, RS
    DESHPANDE, HR
    EXPERIENTIA, 1979, 35 (05): : 574 - 574
  • [6] A straightforward synthesis of pyrimido[4,5-b]quinoline derivatives assisted by microwave irradiation
    Quiroga, Jairo
    Trilleras, Jorge
    Insuasty, Braulio
    Abonia, Rodrigo
    Nogueras, Manuel
    Marchal, Antonio
    Cobo, Justo
    TETRAHEDRON LETTERS, 2010, 51 (07) : 1107 - 1109
  • [7] PYRIMIDO [4,5-B]PYRAZINES .2. 2,4-DIAMINOPYRIMIDO [4,5-B]PYRAZINE AND DERIVATIVES
    MALLETTE, MF
    TAYLOR, EC
    CAIN, CK
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1947, 69 (07) : 1814 - 1816
  • [8] Recent Routes in Synthesis and Biological Activity of Pyrimido[4,5-b] Quinoline Derivatives: A Review (Part II)
    Abu-Hashem, Ameen A.
    Hakami, Othman
    Amri, Nasser
    Ameen, Tahah A.
    Bajaber, Majed A.
    Youssef, Mohammed M.
    Gouda, Moustafa A.
    MINI-REVIEWS IN ORGANIC CHEMISTRY, 2025, 22 (03) : 340 - 358
  • [9] NOVEL SYNTHESIS OF PYRIMIDO[4,5-B]QUINOLINE-2(3H),4(10H)-DIONES (5-DEAZAFLAVINS)
    MORI, K
    SHINOZUKA, K
    SAKUMA, Y
    YONEDA, F
    JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1978, (17) : 764 - 764
  • [10] DEHYDROGENATION OF ALCOHOLS BY PYRIMIDO[4,5-B]QUINOLINE-2(3H),4(10H)-DIONE (5-DEAZAFLAVIN)
    YONEDA, F
    SAKUMA, Y
    HEMMERICH, P
    JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1977, (22) : 825 - 826
12345