Development of QSAR model for prediction of fold selectivity of phenyl benzoxazole as estrogen receptor inhibitors
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QSAR model development of 37 phenyl benzoxazole was carried out to predict the fold selectivity for estrogen receptor. The ratio of IC50 for estrogen receptor-α and estrogen receptor-β (fold selectivity) was taken as biological activity. Physicochemical parameters were calculated using Dragon software, version 1.11. Sequential multiple linear regression analysis was carried out to derive QSAR models, which were further evaluated for statistical significance and predictive power by internal and external validation. The best quantitative structure activity relationship model was selected having a correlation coefficient (R 2) of 0.948, cross-validated correlation coefficient (Q 2) of 0.921, and R pred 2 of 0.853. The predictive ability of the selected model was also confirmed by leave one-out cross-validation. The QSAR model indicates that the descriptors (H1p, R5u, RTe) play an important role in estrogen receptor-β binding. The information generated from this study may be useful in the design of more potent substituted phenyl benzoxazole derivatives as estrogen receptor ligands.
KeywordsQSAR Phenyl benzoxazole Estrogen receptor Sequential linear regression Fold selectivity GETAWAY descriptors
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