3,5-Disubstituted-thiazolidine-2,4-dione analogs as anticancer agents: Design, synthesis and biological characterization

作者：Liu Kai; Rao Wei; Parikh Hardik; Li Qianbin; Guo Tai L; Grant Steven; Kellogg Glen E; Zhang Shijun^*

来源：European Journal of Medicinal Chemistry, 2012, 47: 125-137.

DOI：10.1016/j.ejmech.2011.10.031

• Thiazolidine-2,4-dione
• Anticancer
• Signaling pathways
• Apoptosis
• Multitarget molecule

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.

• 出版日期2012-1