Article

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

Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
European journal of medicinal chemistry (impact factor: 3.27). 10/2011; 47(1):125-37. DOI:10.1016/j.ejmech.2011.10.031 pp.125-37
Source: PubMed

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.

0 0
 · 
0 Bookmarks
 · 
44 Views
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

anti-proliferative activities
 
anti-proliferative activity
 
anticancer agents
 
arrest U937 cells
 
DU145 cancer cells
 
ERK
 
identified lead 1
 
induce apoptosis
 
kinase
 
multi-target properties
 
phosphatidylinositol 3-kinase
 
PI3K)/Akt signaling cascades
 
potential anticancer agent
 
Raf/MEK/ERK
 
Raf/MEK/extracellular signal
 
Western blot analysis