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

Abstract

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.

• Authors: Romeo Romagnoli, Pier Giovanni Baraldi, Maria Kimatrai Salvador, M Encarnacion Camacho, Jan Balzarini, Jaime Bermejo, Francisco Estévez
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 63 Pg. 544-57 (May 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23537942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• 5-benzylidene thiazolidine-2,4-dione
• Antineoplastic Agents
• Benzylidene Compounds
• Thiazolidinediones
• thiazolidine-2,4-dione
• Cytochromes c
• Caspases

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Benzylidene Compounds (chemical synthesis, chemistry, pharmacology)
• Blotting, Western
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cytochromes c (metabolism)
• DNA Fragmentation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Flow Cytometry
• HL-60 Cells
• HeLa Cells
• Humans
• Mice
• Microscopy, Fluorescence
• Models, Chemical
• Molecular Structure
• Thiazolidinediones (chemical synthesis, chemistry, pharmacology)
• U937 Cells