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

Author(s): Xiaoxue Dou, Xin Li, Liu Tao, Chunqi Hu, Lei Zhang, Qiaojun He, Bo Yang, Yongzhou Hu.

Journal Name: Medicinal Chemistry

Volume 9 , Issue 4 , 2013

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Abstract:

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 μM to 9.0 μM.

Keywords: Cytotoxic activity, MDM2 E3 ligase inhibitory activity, p53-MDM2 binding inhibitor, pyrimido[4, 5-b]quinoline- 2, 4-dione

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Article Details

VOLUME: 9
ISSUE: 4
Year: 2013
Page: [581 - 587]
Pages: 7
DOI: 10.2174/1573406411309040012
Price: $58

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