Details

Autor(en) / Beteiligte

• Chilin, Adriana
• Battistutta, Roberto
• Bortolato, Andrea
• Cozza, Giorgio
• Zanatta, Samuele
• Poletto, Giorgia
• Mazzorana, Marco
• Zagotto, Giuseppe
• Uriarte, Eugenio
• Guiotto, Adriano
• Pinna, Lorenzo A
• Meggio, Flavio
• Moro, Stefano

Titel

Coumarin as Attractive Casein Kinase 2 (CK2) Inhibitor Scaffold: An Integrate Approach To Elucidate the Putative Binding Motif and Explain Structure–Activity Relationships

Ist Teil von

• Journal of medicinal chemistry, 2008-02, Vol.51 (4), p.752-759

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

2008

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Casein kinase 2 (CK2) is an ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Recently, using different virtual screening approaches, we have identified several novel CK2 inhibitors. In particular, we have discovered that coumarin moiety can be considered an attractive CK2 inhibitor scaffold. In the present work, we have synthetized and tested a small library of coumarins (more than 60), rationalizing the observed structure–activity relationship. Moreover, the most promising inhibitor, 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC), has been also crystallized in complex with CK2, and the experimental binding mode has been used to derive a linear interaction energy (LIE) model.