Archives of Pharmacal Research

  • 제29권11호
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  • Pages.969-976
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  • 2006
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

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)
  • 발행 : 2006.11.30
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초록

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.

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참고문헌

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