Structural requirement of isoflavonones for the inhibitory activity of interleukin-5.
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 microM, IC(50)=15.3 microM) 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.
Jung
Sang-Hun
SH
College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea. jungshh@cnu.ac.kr
Cho
Soo-Hyun
SH
Dang
The Hung
TH
Lee
Jee-Hyun
JH
Ju
Jung-Hun
JH
Kim
Mi-Kyung
MK
Lee
Seung-Ho
SH
Ryu
Jae-Chun
JC
Kim
Youngsoo
Y
D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D007529:Isoflavones / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D013329:Structure-Activity Relationship
D001578:Benzopyrans; D006027:Glycosides; D015848:Interleukin-5; D007529:Isoflavones; C120642:sophoricoside