Tyrosine kinase inhibitors from the rainforest tree Polyscias murrayi.
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.
Buchanan
Malcolm S
MS
Natural Product Discovery, Eskitis Institute, Griffith University, Brisbane, Qld. 4111, Australia.
Carroll
Anthony R
AR
Edser
Annette
A
Parisot
John
J
Addepalli
Rama
R
Quinn
Ronald J
RJ
D027481:Araliaceae / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011891:Rain; D014197:Trees / Q000737:chemistry*
D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases