Anticancer activity of novel hybrid molecules containing 5-benzylidene thiazolidine-2,4-dione

作者：Romagnoli Romeo^*; Baraldi Pier Giovanni; Salvador Maria Kimatrai; Camacho M Encarnacion; Balzarini Jan; Bermejo Jaime; Estevez Francisco

来源：European Journal of Medicinal Chemistry, 2013, 63: 544-557.

DOI：10.1016/j.ejmech.2013.02.030

• Apoptosis
• Structure-activity relationship
• Thiazolidine-2,4-dione
• In vitro antiproliferative activity
• Caspases

Hybridization of two different bioactive molecules with different mechanism of action is one of the methods that are being adopted to treat cancer. Molecules bearing a thiazolidine-2,4-dione scaffold have been recognized as antineoplastic agents with a broad spectrum of activity against many cancer cell lines. In this manuscript we have described the synthesis and biological evaluation of two series of N-3-substituted-5-arylidene thiazolidine-2,4-diones, bearing the alpha-bromoacryloylamido moiety at the para- or meta-position on the phenyl of the arylidene portion. We have observed that selected compounds 5a, 5c and 5g suppress proliferation of human myeloid leukaemia HL-60 and U937 cells by triggering morphological changes and internucleosomal DNA fragmentation, which are well-known features of apoptosis. Finally, our results indicated that the investigated compounds induced apoptotic cell death through a mechanism that involved activation of multiple caspases and was also associated with the release of cytochrome c from the mitochondria.

• 出版日期2013-5
• 单位河北医科大学