Details

Autor(en) / Beteiligte

• Turrado, Carlos
• Puig, Teresa
• García-Cárceles, Javier
• Artola, Marta
• Benhamú, Bellinda
• Ortega-Gutiérrez, Silvia
• Relat, Joana
• Oliveras, Gloria
• Blancafort, Adriana
• Haro, Diego
• Marrero, Pedro F
• Colomer, Ramón
• López-Rodríguez, María L

Titel

New Synthetic Inhibitors of Fatty Acid Synthase with Anticancer Activity

Ist Teil von

• Journal of medicinal chemistry, 2012-06, Vol.55 (11), p.5013-5023

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Fatty acid synthase (FASN) is a lipogenic enzyme that is highly expressed in different human cancers. Here we report the development of a new series of polyphenolic compounds 5–30 that have been evaluated for their cytotoxic capacity in SK-Br3 cells, a human breast cancer cell line with high FASN expression. The compounds with an IC50 < 50 μM have been tested for their ability to inhibit FASN activity. Among them, derivative 30 blocks the 90% of FASN activity at low concentration (4 μM), is highly cytotoxic in a broad panel of tumor cells, induces apoptosis, and blocks the activation of HER2, AKT, and ERK pathways. Remarkably, 30 does not activate carnitine palmitoyltransferase-1 (CPT-1) nor induces in mice weight loss, which are the main drawbacks of other previously described FASN inhibitors. Thus, FASN inhibitor 30 may aid the validation of this enzyme as a therapeutic target for the treatment of cancer.