Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
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Pharmacophore Based Comparative Molecular Field Analysis of CRTh2 Antagonists

  • Babu, Sathya (Department of Bioinformatics, School of Bioengineering, SRM University) ;
  • Madhavan, Thirumurthy (Department of Bioinformatics, School of Bioengineering, SRM University)
  • Received : 2015.04.22
  • Accepted : 2015.06.25
  • Published : 2015.06.30
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Abstract

Chemoattractant receptor homologous molecule expressed on Th2 cells (CRTh2) is a G-protein coupled receptor targeted for inflammatory diseases such as asthma, allergic rhinitis and atopic dermatitis. In this study, pharmacophore modeling and comparative molecular field analysis (CoMFA) were performed on the series of 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl) acetic acids derivatives. Five highly active compounds were used for generation of pharmacophore models using GASP module. The best pharmacophore model was selected and used as template for the alignment of compounds which was used for CoMFA analysis. The best predictions obtained for CoMFA was $q^2=0.545$, $r^2=0.756$. The predictive ability of the model was investigated using 15 test set compounds. Contour maps suggested that presence of bulky substituents at $5^{th}$ position of benzene ring connected to suphur atoms attached to imidazol ring will increase the activity of the compounds. The results obtained from this study will be useful to design more potent CRTh2 antagonists.

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