New Synthetic Inhibitors
of Fatty Acid Synthase with
Anticancer Activity
- Publication date
- Publisher
Abstract
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 <b>5</b>–<b>30</b> 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 IC<sub>50</sub> < 50 μM have been tested
for their ability to inhibit FASN activity. Among them, derivative <b>30</b> 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, <b>30</b> 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 <b>30</b> may aid the validation of this enzyme as a therapeutic
target for the treatment of cancer
