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3D-QSAR Studies of JNK1 Inhibitors Utilizing Various Alignment Methods.
MedLine Citation:
PMID:  21722320     Owner:  NLM     Status:  Publisher    
We report our three-dimensional quantitative structure activity relationship (3D-QSAR) studies of the series of anilinopyrimidine derivatives of JNK1 inhibitors. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied using different alignment methods. The ligand-based atom-by atom matching alignment has produced better values for CoMFA (q(2) =0.646 and r(2) =0.983), while in CoMSIA it has achieved only lower statistical values. The pharmacophore-based model has produced (q(2) = 0.568, r(2) = 0.938) and (q(2) =0.670, r(2) = 0.982) for CoMFA and CoMSIA models, respectively. As the model was based on the receptor-guided alignment, all the compounds were optimized within the receptor, resulting in q(2) = 0.605 and r(2) = 0.944 for CoMFA, and q(2) = 0.587 and r(2) = 0.863 for CoMSIA. Molecular Dynamic simulation studies suggested that the generated models were consistent with the low energy protein ligand conformation. The CoMFA and CoMSIA contour maps indicated that the substitutions of the electropositive groups in the phenyl ring, and an addition of hydrophobic groups in the pyrimidine ring, are important to enhance the activity of this series. Moreover, the virtual screening analysis against NCI database yields potentials hits and the results obtained would be useful to synthesize selective and highly potent JNK1 analogs.
Thirumurthy Madhavan; Jae Yoon Chung; Gugan Kothandan; Changdev G Gadhe; Seung Joo Cho
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-1
Journal Detail:
Title:  Chemical biology & drug design     Volume:  -     ISSN:  1747-0285     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101262549     Medline TA:  Chem Biol Drug Des     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 John Wiley & Sons A/S.
Department of Bio New Drug Development, College of Medicine, Chosun University, 375 Seosuk-dong, Dong-gu Gwangju 501-759, Korea Life/Health Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang,Seoul 130-650, Republic of Korea Department of Cellular and Molecular Medicine, College of Medicine, Chosun University, 375 Seosuk-dong, Dong-gu Gwangju 501-759, Korea.
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