Journal of Integrative Natural Science (통합자연과학논문집)

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

  • Babu, Sathya (Department of Bioinformatics, Center for Plant Molecular Biology and Biotechnology, Agricultural College and Research Institute, Tamil Nadu Agricultural University)
  • Received : 2015.11.28
  • Accepted : 2015.12.25
  • Published : 2015.12.30
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Abstract

Chemoattractant Receptor Homologous molecule expressed on Th2 cells (CRTh2) is a chemoattractant receptor with seven transmembrane helices targeted for inflammatory diseases such as asthma and allergic rhinitis. In this study, pharmacophore based Comparative Molecular Similarity Indices Analysis (CoMSIA) were performed on the series of 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl) acetic acids derivatives. Initially, GASP module was used for generation of pharmacophore models using five highly active compounds from the dataset. Among the generated pharmacophores, the best pharmacophore model was selected based on fitness score and was used as template for the alignment of compounds which was used for CoMSIA analysis. The best predictions were obtained utilizing steric, hydrophobic and H-bond acceptor parameters showing a $q^2$=0.559 and $r^2$=0.730. 15 test set compounds was used to investigate the predictive ability of the CoMSIA model. Contour maps suggested that presence of bulky substituents and H-bond acceptor atoms at $5^{th}$ position of benzene 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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References

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