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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. February 2008, Volume 7, Number 2, 38-46 |
3D-QSAR (Quantitative Structure-Activity Relationships) Studies on Urea Derivatives as Inhibitors of p38 MAP Kinase
Rituparna Sarma, Sharat Sinha, Muttineni Ravikumar, Madala Kishore Kumar, and Shaik Mahmood
Internet Electron. J. Mol. Des. 2008, 7, 38-46
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Abstract:
Inhibition of the p38 MAP kinase pathway has been shown to be beneficial in the
treatment of inflammatory diseases. A three-dimensional quantitative structure-activity
relationship (3D-QSAR) model, based on molecular field analysis
(MFA), was developed for 41 urea derivatives that are inhibitors of p38 mitogen-activated
protein kinase (p38 MAPK). The 3D-QSAR model was developed using
32 compounds and its predictive ability was assessed using a test set of 9
compounds. MFA studies were performed using the QSAR module of Cerius2.
The predictive 3D-QSAR model has a conventional r2 = 0.901 and a cross-validated
coefficient r2cv = 0.799. The model was able to efficiently predict the
activities of the compounds of the test set (r2pred = 0.740),
suggesting that it can be
used for the development of new p38 MAPK inhibitor candidates, useful for
treatment of chronic inflammatory states. The structural features indicated by this
3D-QSAR analysis provide a helpful guideline to design novel compounds with
inhibitory activities against p38 MAPK.
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