Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
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A CoMFA Study of Phenoxypyridine-Based JNK3 Inhibitors Using Various Partial Charge Schemes

  • Balasubramanian, Pavithra K. (Department of Bio-New Drug Development, College of Medicine, Chosun University) ;
  • Balupuri, Anand (Department of Bio-New Drug Development, College of Medicine, Chosun University) ;
  • Cho, Seung Joo (Department of Bio-New Drug Development, College of Medicine, Chosun University)
  • Received : 2014.03.05
  • Accepted : 2014.03.25
  • Published : 2014.03.30
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Abstract

The (c-Jun N-terminal kinase 3) JNK3 is a potential therapeutic target for various neurological disorders. Here, a three dimensional quantitative structure-activity relationship (3D-QSAR) study on phenoxypyridine as JNK3 inhibitors was performed to rationalize the structural requirements responsible for the inhibitory activity of these compounds. The comparative molecular field analysis (CoMFA) using different partial atomic charges, was employed to understand the structural factors affecting JNK3 inhibitory potency. The Gasteiger-Marsili yielded a CoMFA model with cross-validated correlation coefficient ($q^2$) of 0.54 and non-cross-validated correlation coefficient ($r^2$) of 0.93 with five components. Furthermore, contour maps suggested that bulky substitution with oxygen atom in $R^3$ position could enhance the activity considerably. The work suggests that further chemical modifications of the compounds could lead to enhanced activity and could assist in the design of novel JNK3 inhibitors.

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References

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