Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/72804
Título: Synthesis and Biological Evaluation of 2-Substituted Benzyl-/Phenylethylamino-4-amino-5-aroylthiazoles as Apoptosis-Inducing Anticancer Agents
Autores/as: Oliva, Paola
Onnis, Valentina
Balboni, Elisa
Hamel, Ernest
Estévez-Sarmiento, Francisco
Quintana Aguiar, José Martín 
Estévez Rosas, Francisco Jesús 
Brancale, Andrea
Ferla, Salvatore
Manfredini, Stefano
Romagnoli, Romeo
Clasificación UNESCO: 320713 Oncología
Palabras clave: Antiproliferative Activity
Apoptosis
Microtubules
Pharmacophoric Merging
Structure-Activity Relationship
Fecha de publicación: 2020
Publicación seriada: Molecules 
Resumen: Induction of apoptosis is a common chemotherapeutic mechanism to kill cancer cells The thiazole system has been reported over the past decades as a building block for the preparation of anticancer agents. A novel series of 2-arylalkylamino-4-amino-5-(3',4',5'-trimethoxybenzoyl)-thiazole derivatives designed as dual inhibitors of tubulin and cyclin-dependent kinases (CDKs) were synthesized and evaluated for their antiproliferative activity in vitro against two cancer cell lines and, for selected highly active compounds, for interactions with tubulin and cyclin-dependent kinases and for cell cycle and apoptosis effects. Structure-activity relationships were elucidated for various substituents at the 2-position of the thiazole skeleton. Among the synthesized compounds, the most active analogues were found to be the p-chlorobenzylamino derivative 8e as well as the p-chloro and p-methoxyphenethylamino analogues 8f and 8k, respectively, which inhibited the growth of U-937 and SK-MEL-1 cancer cell lines with IC50 values ranging from 5.7 to 12.2 μM. On U-937 cells, the tested compounds 8f and 8k induced apoptosis in a time and concentration dependent manner. These two latter molecules did not affect tubulin polymerization (IC50 > 20 μM) nor CDK activity at a single concentration of 10 μM, suggesting alternative targets than tubulin and CDK for the compounds.
URI: http://hdl.handle.net/10553/72804
ISSN: 1420-3049
DOI: 10.3390/molecules25092177
Fuente: Molecules (Basel, Switzerland ) [EISSN 1420-3049], v. 25 (9), (Mayo 2020)
Colección:Artículos
miniatura
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