Structural Requirement of Isoflavonones for the Inhibitory Activity of Interleukin-5.

Abstract Sophoricoside isolated from Sophora japonica is a glycoside of isoflavonone as an inhibitor of interleukin (IL)-5. To identify structural requirements of this isoflavonone for its inhibitory activity against IL-5, isoflavonones, isoflavanones, and their glycosides were prepared and their inhibitory activity was tested against IL-5. Among them, 5-benzyloxy-3-(4-hydroxyphenyl)chromen-4-one ( 4b , 87.9% inhibition at 50 μM, IC 50 =15.3 μM) shows the most potent activity, comparable with that of sophoricoside. The important structural requirements of these isoflavonone analogs exhibiting the inhibitory activity against IL-5 were recognized as (1) planarity of chromen-4-one ring, (2) existence of phenolic hydroxyl at 4-position of B ring, and (3) introduction of benzyloxy at 5-position, which may act as a bulky group for occupying hydrophobic pocket in putative binding site. However the glucopyranosyl moiety of sophoricoside is not an essential motif for the activity.