|Title:||Hybrid molecules containing benzo[4,5]imidazo[1,2-d][1,2,4]thiadiazole and alpha-bromoacryloyl moieties as potent apoptosis inducers on human myeloid leukaemia cells||Authors:||Romagnoli, Romeo
Baraldi, Pier Giovanni
Carrion, Maria Dora
Tabrizi, Mojgan Aghazadeh
Distamycin, et al
|Issue Date:||2007||Publisher:||0960-894X||Project:||Nuevos Compuestos Antileucémicos||Journal:||Bioorganic and Medicinal Chemistry Letters||Abstract:||The synthesis and biological activity of a series of hybrids 1-5 prepared combining a benzo[4,5]imidazo[1,2-d][1,2,4]thiadiazole and different benzoheterocyclic α-bromoacryloyl amides have been described and their structure-activity relationships discussed. All these hetero-bifunctional compounds were highly cytotoxic against the human myeloid leukaemia cell lines HL-60 and U937 (IC50 0.24-1.72 μM), significantly superior to that of both alkylating units alone. In human myeloid leukaemia HL-60 cells we observed that these compounds suppress survival and proliferation by triggering morphological changes and internucleosomal DNA fragmentation characteristic of apoptotic cell death. The apoptosis induced by these compounds is mediated by caspase-3 activation and is also associated to an early release of cytochrome c from the mitochondria. © 2007 Elsevier Ltd. All rights reserved.||URI:||http://hdl.handle.net/10553/50567||ISSN:||0960-894X||DOI:||10.1016/j.bmcl.2007.02.048||Source:||Bioorganic & Medicinal Chemistry Letters[ISSN 0960-894X],v. 17 (10), p. 2844-2848|
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