title: The role of the hydrophobic group on ring A of chalcones in the inhibition of interleukin-5.
abstract: Novel chalcones were found as potent inhibitors of interleukin-5 (11-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at 50 microM, IC50 = 25.3 microM) was initially identified as a potent inhibitor of IL-5. This activity is comparable to that of budesonide or sophoricoside (1a). The benzyloxy group appears to be critical for the enhancement of the IL-5 inhibitory activity. To identify the role of this hydrophobic moiety, cyclohexyloxy (2d), cyclohexylmethoxy (2c), cyclohexylethoxy (2e), cyclohexylpropoxy (2f), 2-methylpropoxy (2g), 3-methylbutoxy (2h), 4-methylpentoxy (2i), and 2-ethylbutoxy (2j) analogs were prepared and tested for their effects on IL-5 bioactivity. Compounds 2c (IC50 = 12.6 microM), 2d (IC50 = 12.2 microM), and 2i (IC50 = 12.3 microM) exhibited the most potent activity. Considering the cLog P values of 2, the alkoxy group contributes to the cell permeability of 2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of 2 should be one that provides the cLog P of 2 in the range of 4.22 to 4.67.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, 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: Gyu-Yong
authors.initials: GY
authors.lastname: Song
authors.forename: In-Jeong
authors.initials: IJ
authors.lastname: Lee
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: D002460:Cell Line; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007202:Indicators and Reagents; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D047188:Chalcones; D007202:Indicators and Reagents; D015848:Interleukin-5