1. 3,5-Disubstituted-thiazolidine-2,4-dione analogs as anticancer agents: Design, synthesis and biological characterization
- Author
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Liu, Kai, Rao, Wei, Parikh, Hardik, Li, Qianbin, Guo, Tai L., Grant, Steven, Kellogg, Glen E., and Zhang, Shijun
- Subjects
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THIAZOLIDINEDIONES , *ANTINEOPLASTIC agents , *DRUG design , *ORGANIC synthesis , *DRUG synergism , *CELLULAR signal transduction - Abstract
Abstract: A series of 2,5-disubstituted-thiazolidine-2,4-dione analogs based on the newly identified lead 1, a potential anticancer agent via the inhibition of the Raf/MEK/extracellular signal regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascades, were synthesized and biologically characterized. A new lead structure, 15, was identified to have improved anti-proliferative activities in U937 cells, to induce apoptosis in U937, M12 and DU145 cancer cells, and to arrest U937 cells at the S-phase. Furthermore, Western blot analysis demonstrated a correlation of the anti-proliferative activity and blockade of the Raf/MEK/ERK and PI3K/Akt signaling pathways. Collectively, these results strongly encourage further optimization of 15 as a new lead with multi-target properties to develop more potent compounds as anticancer agents. [Copyright &y& Elsevier]
- Published
- 2012
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