Neuroblastoma (NB) represents the most common extracranial paediatric solid tumor for which no specific FDA-approved treatment is currently available. The tyrosine kinase c-Src has been reported to play an important role in the differentiation, cell-adhesion and survival of NB cells. Starting from dual Src/Abl inhibitors previously found active in NB cell lines (1-3), small modification of the original structures almost abolished the Abl activity with a contemporary improvement of affinity and specificity for c-Src. Among the synthesized compounds, the most potent c-Src inhibitor (10a) showed a very interesting antiproliferative activity in SH-SY5Y cells with an IC(50) of 80 nM and a favourable ADME profile. A 3D SAR analysis was also attempted and may guide the design of more potent c-Src inhibitors as potential agents for NB treatment.

Identification of Potent c-Src Inhibitors Strongly Affecting the Proliferation of Human Neuroblastoma Cells / Radi, Marco; Chiara, Brullo; Emmanuele, Crespan; Cristina, Tintori; Francesca, Musumeci; Mariangela, Biava; Silvia, Schenone; Elena, Dreassi; Claudio, Zamperini; Giovanni, Maga; Dafne, Pagano; Adriano, Angelucci; Mauro, Bologna; Maurizio, Botta. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 21:(2011), pp. 5928-5933. [10.1016/j.bmcl.2011.07.079]

Identification of Potent c-Src Inhibitors Strongly Affecting the Proliferation of Human Neuroblastoma Cells

RADI, Marco;
2011-01-01

Abstract

Neuroblastoma (NB) represents the most common extracranial paediatric solid tumor for which no specific FDA-approved treatment is currently available. The tyrosine kinase c-Src has been reported to play an important role in the differentiation, cell-adhesion and survival of NB cells. Starting from dual Src/Abl inhibitors previously found active in NB cell lines (1-3), small modification of the original structures almost abolished the Abl activity with a contemporary improvement of affinity and specificity for c-Src. Among the synthesized compounds, the most potent c-Src inhibitor (10a) showed a very interesting antiproliferative activity in SH-SY5Y cells with an IC(50) of 80 nM and a favourable ADME profile. A 3D SAR analysis was also attempted and may guide the design of more potent c-Src inhibitors as potential agents for NB treatment.
2011
Identification of Potent c-Src Inhibitors Strongly Affecting the Proliferation of Human Neuroblastoma Cells / Radi, Marco; Chiara, Brullo; Emmanuele, Crespan; Cristina, Tintori; Francesca, Musumeci; Mariangela, Biava; Silvia, Schenone; Elena, Dreassi; Claudio, Zamperini; Giovanni, Maga; Dafne, Pagano; Adriano, Angelucci; Mauro, Bologna; Maurizio, Botta. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 21:(2011), pp. 5928-5933. [10.1016/j.bmcl.2011.07.079]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2432130
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