Yang Hyun-Mo, Shin Hye-Rim, Cho Soo-Hyun, Bang Seong-Cheol, Song Gyu-Yong, Ju Jung-Hun, Kim Mi-Kyeong, Lee Seung-Ho, Ryu Jae-Chun, Kim Youngsoo, Jung Sang-Hun
College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
Bioorg Med Chem. 2007 Jan 1;15(1):104-11. doi: 10.1016/j.bmc.2006.10.007. Epub 2006 Oct 10.
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.
新型查尔酮被发现是白细胞介素（IL）-5的有效抑制剂。1-(2-苄氧基-6-羟基苯基)-3-(4-羟基苯基)-2-丙烯-1-酮（2b，在50μM时抑制率为78.8%，IC50=25.3μM）最初被鉴定为IL-5的有效抑制剂。这显示出与布地奈德或槐糖苷具有相当的活性。为了确定结构要求，制备了26种查尔酮，并测试了它们对IL-5的抑制活性。其中，化合物4-[(E)-3-(2-环己基甲氧基-6-羟基苯基)-3-氧代丙-1-烯基]苯磺酰胺（2w，在50μM时抑制率为99.5%，IC50=1.8μM）表现出最强的活性。这些对IL-5具有抑制活性的查尔酮类似物的重要结构要求如下：（1）A环6位的疏水基团如苄氧基或环己基甲氧基是必需的。（2）A环6位存在酚羟基至关重要。（3）作为α,β-不饱和酮的丙烯酮单元是必不可少的。（4）B环4位具有氢受体性质的吸电子基团增强活性，并确定了关于这些取代基的2的定量构效关系。
