Structural requirement of chalcones for the inhibitory activity of interleukin-5.
Novel chalcones were found as potent inhibitors of interleukin (IL)-5. 1-(2-Benzyloxy-6-hydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one (2b, 78.8% inhibition at 50microM, IC(50)=25.3microM) was initially identified as a potent inhibitor of IL-5. This shows the compatible activity with budesonide or sophoricoside. To identify structural requirements, 26 chalcones were prepared and their inhibitory activities were tested against IL-5. Among them, compound 4-[(E)-3-(2-cyclohexylmethoxy-6-hydroxyphenyl)-3-oxoprop-1-enyl]benzenesulfonamide (2w, 99.5% inhibition at 50microM, IC(50)=1.8microM) shows the most potent activity. The important structural requirements of these chalcone analogs exhibiting the inhibitory activity against IL-5 were recognized as the following. (1) The hydrophobic group such as benzyloxy or cyclohexylmethoxy at 6-position of A ring is necessary. (2) The existence of phenolic hydroxyl at 6-position of A ring is critical. (3) Propenone unit as alpha,beta-unsaturated ketone is essential. (4) Electron withdrawing groups with hydrogen acceptor property at 4-position of B ring enhance the activity and quantitative structure-activity relationship of 2 regarding these substituents was determined.
Yang
Hyun-Mo
HM
College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
Shin
Hye-Rim
HR
Cho
Soo-Hyun
SH
Bang
Seong-Cheol
SC
Song
Gyu-Yong
GY
Ju
Jung-Hun
JH
Kim
Mi-Kyeong
MK
Lee
Seung-Ho
SH
Ryu
Jae-Chun
JC
Kim
Youngsoo
Y
Jung
Sang-Hun
SH
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D047188:Chalcones; D015848:Interleukin-5