Azastilbenes: a cut-off to p38 MAPK inhibitors?

Organic & Biomolecular Chemistry Pub Date: 2013-05-14 DOI: 10.1039/C3OB27449G

Abstract

Inhibitors with vicinal 4-fluorophenyl/4-pyridine rings on a five- or six-membered heterocyclic ring are known to inhibit the p38 mitogen-activated protein kinase (MAPK), which is a potential target for rheumatoid arthritis and several different types of cancer. Several substituted azastilbene-based compounds with vicinal 4-fluorophenyl/4-pyridine rings were designed using computational docking, synthesized, and evaluated in a cell-free radiometric p38α assay. The biochemical evaluation shows that the best inhibition (down to 110 nM) is achieved for azastilbene-based compounds having an isopropylamine substituent in the 2-position of the pyridine ring. The inhibition of p38 signaling in human breast cancer cells was observed for two of the compounds.

Graphical abstract: Azastilbenes: a cut-off to p38 MAPK inhibitors
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