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Design and synthesis of novel furoquinoline based inhibitors of multiple targets in the PI3K/Akt-mTOR pathway

  作者 Lohar, MV; Mundada, R; Bhonde, M; Padgaonkar, A; Deore, V; Yewalkar, N; Bhatia, D; Rathos, M; Joshi, K; Vishwakarma, RA; Kumar, S  
  选自 期刊  Bioorganic & Medicinal Chemistry Letters;  卷期  2008年18-12;  页码  3603-3606  
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[摘要]We herein report the design and synthesis of furoquinoline based novel molecules (16-36) and their in vitro multiple targeted inhibitory potency against PI3K/Akt phosphorylation and mTOR using cell based and cell-free kinase assay. In particular, compound 23 in addition to PI3K-mTOR inhibitory potency, it has shown potent inhibition of hypoxia-induced accumulation of HIF-1 alpha protein in U251-HRE cell line. The inhibitory activities of compound 23 were confirmed by Western blot analysis, using human non-small cell lung carcinoma H-460 cell line and glioblastoma U251 cell lines. (C) 2008 Elsevier Ltd. All rights reserved.

 
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