|
|||||
|
|
α‐Bromoacrylamido N‐Substituted Isatin Derivatives as Potent Inducers of Apoptosis in Human Myeloid Leukemia Cells |
|
| Authors: | Romeo Romagnoli Dr. Pier Giovanni Baraldi Prof. Olga Cruz‐Lopez Dr. Delia Preti Jaime Bermejo Prof. Francisco Estévez Prof. |
| Affiliation: | 1. Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara (Italy), Fax: (+39)?(0)532‐455953;2. Instituto de Productos Naturales y Agrobiología, CSIC, Instituto Universitario de Bio‐Orgánica “Antonio González”, Universidad de La Laguna, Instituto Canario de Investigación del Cáncer, 38206 La Laguna, Tenerife (Spain);3. Department of Biochemistry, University of Las Palmas de Gran Canaria and Instituto Canario de Investigación del Cáncer, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain) |
| Abstract: | A novel series of α‐bromoacryloyl N‐substituted isatin analogues were found to inhibit the growth and viability of human myeloid leukemia HL‐60 and U‐937 cells as well as human lymphoid leukemia MOLT‐3 cells. Cell death induced by these molecules was preceded by a rapid release of cytochrome c from mitochondria into the cytosol and subsequent caspase activation involving caspase‐3, to cleave poly(ADP‐ribose) polymerase (PARP). These findings suggest that these compounds present antiproliferative activity which may be mediated by apoptosis caused by cytochrome c release and caspase activation in human leukemia cells. |
| Keywords: | antiproliferative agents antitumor agents apoptosis drug design structure– activity relationships |