Tyrosine kinase inhibitors from the rainforest tree Polyscias murrayi

Abstract

A series of 3-(4-hydroxyphenyl) propanoic acid derivatives, which inhibit Itk (interleukin-2 inducible T-cell kinase), a Th2-cell target, were isolated from the Australian rainforest tree Polyscias murrayi. The new compound 3-(4-hydroxyphenyl) propionyl choline and a 2:1 mixture of the new compounds 3,4-di-O-3-(4-hydroxyphenyl) propionyl-1,5-dihydroxycyclohexanecarboxylic acid and 3,5-di-O-3-(4-hydroxyphenyl) propionyl-1,4-dihydroxycyclohexanecarboxylic acid were isolated along with two known compounds 3-(4-hydroxyphenyl) propanoic acid and 3-(3,4-hydroxyphenyl) propanoic acid. Their structures were determined by 1D and 2D NMR spectroscopy. The assay results suggest that both the 3-(4-hydroxyphenyl) propanoate and carboxyl moieties contribute to Itk activity of the compounds.