title: Structural requirement of chalcones for the inhibitory activity of interleukin-5.
abstract: 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.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Yang
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Shin
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Cho
authors.forename: Seong-Cheol
authors.initials: SC
authors.lastname: Bang
authors.forename: Gyu-Yong
authors.initials: GY
authors.lastname: Song
authors.forename: Jung-Hun
authors.initials: JH
authors.lastname: Ju
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Jae-Chun
authors.initials: JC
authors.lastname: Ryu
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Jung
mesh_terms: 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
chemical_list: D047188:Chalcones; D015848:Interleukin-5