Abstract
A successful 3D-QSAR study has been performed for amino-substituted N-acyl and N-aroylpyrazolines as B-Raf kinase inhibitors by means of a common five-point pharmacophore model. In this study, highly predictive 3D-QSAR models have been developed for B-Raf kinase inhibition and pERK inhibition using AADRR-2 and AADRR-6 hypothesis, respectively. The best models showed statistically outstanding values of 0.97, 0.95 and 0.91, 0.87 for r 2 and q 2 for AADRR-2 and AADRR-6 hypothesis, respectively. The validation of the PHASE model was done by dividing the dataset into training and test set. From the QSAR model, it can implicated that electron-withdrawing and hydrophobic groups are not advantageous for both enzymatic and cellular activities. However, H-bond donor characteristic is favorable for cellular inhibition and unfavorable for enzymatic inhibition. Based on the findings of the 3D-QSAR study, novel and promising compounds for B-Raf kinase inhibition can be synthesized.
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The authors wish to acknowledge the team of Schrödinger for providing software facility, UGC for financial support, and Janab Abdul Mueed Sb. for providing infrastructure and facility to carry out this work.
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Tanwar, O., Marella, A., Shrivastava, S. et al. Pharmacophore model generation and 3D-QSAR analysis of N-acyl and N-aroylpyrazolines for enzymatic and cellular B-Raf kinase inhibition. Med Chem Res 22, 2174–2187 (2013). https://doi.org/10.1007/s00044-012-0210-z
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DOI: https://doi.org/10.1007/s00044-012-0210-z