We described the optimization, by molecular modelling, of small pyrazole derivatives, obtained through a 1,3-dipolar cycloaddition between nitrile imines and functionalized acetylenes. The two kinase inhibitors, selected as potential agents active against hepatocellular carcinoma (HCC) were then evaluated in vitro for their biological activity on HCC-derived cell lines. The compounds show an inhibitory growth efficacy (IC50 50–100 M) in SNU449 cell line, as well as block of cell cycle progression and induction of apoptosis, and can be considered as lead compounds for further SAR developments.
Design, Synthesis and Biological Evaluation of Pyrazole derivatives as Potential multikinase Inhibitors in Hepatocarcinoma / F. Fornari; M. Minguzzi; E. Strocchi; E. Locatelli; L. Gramantieri; M. Milazzo; V. Rebuttini; S. Breviglieri; C. M. Camaggi; L. Bolondi; M. Comes Franchini. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 48:(2012), pp. 391-401. [10.1016/j.ejmech.2011.12.031]
Design, Synthesis and Biological Evaluation of Pyrazole derivatives as Potential multikinase Inhibitors in Hepatocarcinoma.
F. Fornari;MINGUZZI, MANUELA;STROCCHI, ELENA;LOCATELLI, ERICA;BOLONDI, LUIGI;COMES FRANCHINI, MAURO
2012
Abstract
We described the optimization, by molecular modelling, of small pyrazole derivatives, obtained through a 1,3-dipolar cycloaddition between nitrile imines and functionalized acetylenes. The two kinase inhibitors, selected as potential agents active against hepatocellular carcinoma (HCC) were then evaluated in vitro for their biological activity on HCC-derived cell lines. The compounds show an inhibitory growth efficacy (IC50 50–100 M) in SNU449 cell line, as well as block of cell cycle progression and induction of apoptosis, and can be considered as lead compounds for further SAR developments.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
