Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 46, Issue 9, Pages 4573-4583Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2011.07.036
Keywords
6-substituted imidazo[1,2-a]pyridines; Multicomponent coupling reactions; Colon cancer; HT-29 and Caco-2; Apoptosis; Caspases
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Funding
- National Research Foundation, Pretoria (NRF) [GUN 2053652]
- IRDP of the NRF (South Africa)
- Research Niche Areas programme
- University of the Witwatersrand (Science Faculty Research Council)
- Mellon Foundation
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A range of 6-substituted imidazo[1,2-a]pyridines were synthesized using a multicomponent coupling reaction. Most of these compounds were found to exhibit excellent activity against the colon cancer cell lines HT-29 and Caco-2, whilst not showing significant toxicity against white blood cells. Our studies have shown that the proteolytic phase of apoptosis was initiated 2 h after treatment with these imidazo [1,2-a]pyridines. The data suggests that the imidazo[1,2-a]pyridine-induced cell death in HT-29 and Caco-2 cells is mediated via pathway(s) that include the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase 3 and caspase 8. (C) 2011 Elsevier Masson SAS. All rights reserved.
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