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The role of the hydrophobic group on ring A of chalcones in the inhibition of interleukin-5

  • Hyun-Mo Yang
  • Hye-Rim Shin
  • Soo-Hyun Cho
  • Gyu-Yong Song
  • In-Jeong Lee
  • Mi-Kyeong Kim
  • Seung-Ho Lee
  • Jae-Chun Ryu
  • Youngsoo Kim
  • Sang-Hun Jung
Articles Drug Design

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 μM, IC50=25.3 μM) 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. Compounds2c (IC50=12.6 μM),2d (IC50=12.2 μM), and2i (IC50=12.3 μM) exhibited the most potent activity. Considering the cLog P values of2, the alkoxy group contributes to the cell permeability of2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of2 should be one that provides the cLog P of2 in the range of 4.22 to 4.67.

Key words

Chalcones Inhibitor Interleukin-5 

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Copyright information

© The Pharmaceutical Society of Korea 2006

Authors and Affiliations

  • Hyun-Mo Yang
    • 1
  • Hye-Rim Shin
    • 1
  • Soo-Hyun Cho
    • 1
  • Gyu-Yong Song
    • 1
  • In-Jeong Lee
    • 2
  • Mi-Kyeong Kim
    • 3
  • Seung-Ho Lee
    • 4
  • Jae-Chun Ryu
    • 5
  • Youngsoo Kim
    • 2
  • Sang-Hun Jung
    • 1
  1. 1.College of PharmacyChungnam National UniversityDaejeonKorea
  2. 2.College of Pharmacy and Research Center for Bioresource and HealthChungbuk National UniversityCheongjuKorea
  3. 3.College of MedicineChungbuk National UniversityCheongjuKorea
  4. 4.College of PharmacyYeungnam UniversityKyungsanKorea
  5. 5.Toxicology LaboratoryKorea Institute of Science and TechnologySeoulKorea

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