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

• DOI: 10.1016/j.ejmech.2013.02.030
• Publication Date: 2013-03-14T01:56:01Z
• Authors: Romeo Romagnoli; Pier Giovanni Bar...; Maria Kimatrai Sa...; M. Encarnacion Ca...; Jan Balzarini; Jaime Bermejo; Francisco Estévez
• Keywords: Cell Survival; Blotting, Western; Brostallicin; Antineoplastic Agents; Apoptosis; HL-60 Cells; DNA Fragmentation; Human Leukemia-Cells; 320713 Oncología; Benzylidene Compounds; Mice; 03 medical and health sciences; Cell Line, Tumor; Mechanisms; Animals; Humans; Cytochrome-C; Inhibition; Cell Proliferation; 0303 health sciences; Dose-Response Relationship, Drug; In vitro antiproliferative activity; Structureeactivity relationship; Cytochromes c; Flow Cytometry; Thiazolidine-2,4-dione; Cancer Cells; 3. Good health; Apoptosis; Caspases; In vitro antiproliferative activity; Structure-activity relationship; Thiazolidine-2,4-dione;; Death; Microscopy, Fluorescence; Models, Chemical; Caspases; Drug Screening Assays, Antitumor; 32 Ciencias médicas; Derivatives; HeLa Cells

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 α-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.