Quantitative structure-activity relationship studies of [(biphenyloxy)propyl]isoxazole derivatives. Inhibitors of human rhinovirus 2 replication |
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Authors: | Kuz'min Victor E Artemenko Anatoly G Muratov Eugene N Volineckaya Ingrid L Makarov Vadim A Riabova Olga B Wutzler Peter Schmidtke Michaela |
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Affiliation: | A.V. Bogatsky Physical-Chemical Institute, Odessa, Ukraine, Research Center for Antibiotics, Moscow, Russia. |
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Abstract: | The 50% cytotoxic concentration (CC50) in HeLa cells, the 50% inhibitory concentration (IC50) against human rhinovirus 2 (HRV-2), and the selectivity index (SI = CC50/IC50) of [(biphenyloxy)propyl]isoxazole derivatives were used to develop quantitative structure-activity relationships (QSAR) based on simplex representation of molecular structure. Statistic characteristics for partial least-squares models are quite satisfactory (R2 = 0.838 - 0.918; Q2 = 0.695 - 0.87) for prediction of CC50, IC50, and SI values and permit the virtual screening and molecular design of new compounds with strong anti-HRV-2 activity. The quality of prognosis for designed compounds was additionally estimated by analysis of domain applicability for each QSAR model. A hypothesis to the effect that terminal benzene substituents must have negative electrostatic potential and definite length (approximately 5.5-5.6 A) to possess strong antiviral activity has been suggested. The quality of developed analysis, i.e., high level of antiviral action of three new designed compounds, has been confirmed experimentally. |
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