통합자연과학논문집 (Journal of Integrative Natural Science)

조선대학교 기초과학연구원 (The Basic Science Institute Chosun University)
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Ligand Based HQSAR Analysis of CRTh2 Antagonists

  • Babu, Sathya (Department of Bioinformatics, School of Bioengineering, SRM University) ;
  • Madhavan, Thirumurthy (Department of Bioinformatics, School of Bioengineering, SRM University)
  • 투고 : 2015.02.03
  • 심사 : 2015.03.25
  • 발행 : 2015.03.30
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초록

CRTh2 receptor is an important mediator of the inflammatory effects and act as beneficial target for the treatment of asthma, COPD, allergic rhinitis and atopic dermatitis. In the present work, Hologram QSAR studies were conducted on a series of 50 training set CRTh2 antagonists (2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl acetic acids). The best HQSAR model was obtained using atoms, bonds, connections and donor/acceptor as fragment distinction parameter using hologram length 257 and 6 components with fragment size of minimum 7 and maximum 10. Significant cross-validated correlation coefficient ($q^2=0.786$) and non cross-validated correlation coefficients ($r^2=0.954$) were obtained. The model was then used to evaluate the 15 external test compounds which are not included in the training set and the predicted values were in good agreement with the experimental results ($r^2_{pred}=0.739$). Contribution map show that presence of C ring and its substituents makes big contributions for activities. The HQSAR model and analysis from the contribution map could be useful for further design of novel structurally related CRTh2 antagonists.

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참고문헌

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