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The Role of the Hydrophobic Group on Ring A of Chalcones in the Inhibition of Interleukin-5  

Yang, Hyun-Mo (College of Pharmacy, Chungnam National University)
Shin, Hye-Rim (College of Pharmacy, Chungnam National University)
Cho, Soo-Hyun (College of Pharmacy, Chungnam National University)
Song, Gyu-Yong (College of Pharmacy, Chungnam National University)
Lee, In-Jeong (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University)
Kim, Mi-Kyeong (College of Medicine, Chungbuk National University)
Lee, Seung-Ho (College of Pharmacy, Yeungnam University)
Ryu, Jae-Chun (Toxicology Laboratory, Korea Institute of Science and Technology)
Kim, Young-Soo (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University)
Jung, Sang-Hun (College of Pharmacy, Chungnam National University)
Publication Information
Archives of Pharmacal Research / v.29, no.11, 2006 , pp. 969-976 More about this Journal
Abstract
Novel chalcones were found as potent inhibitors of interleukin-5 (II-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at $50\;{\mu}M,\;IC_{50}=25.3\;{\mu}M$) 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 ($IC_{50}=12.6\;{\mu}M$), 2d ($IC_{50}=12.2\;{\mu}M$), and 2i ($IC_{50}=12.3\;{\mu}M$) 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.
Keywords
Chalcones; Inhibitor; Interleukin-5;
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