1. Quantitative Structure−Activity Relationship Studies of [(Biphenyloxy)propyl]isoxazole Derivatives. Inhibitors of Human Rhinovirus 2 Replication
- Author
-
Olga B. Riabova, Peter Wutzler, Ingrid L. Volineckaya, Eugene N. Muratov, Vadim Makarov, Anatoly G. Artemenko, Michaela Schmidtke, and Victor E. Kuz’min
- Subjects
Models, Molecular ,Quantitative structure–activity relationship ,Virtual screening ,Molecular Structure ,Rhinovirus ,biology ,Stereochemistry ,Chemistry ,Quantitative Structure-Activity Relationship ,Ether ,Isoxazoles ,Virus Replication ,biology.organism_classification ,Antiviral Agents ,HeLa ,chemistry.chemical_compound ,Drug Discovery ,Humans ,Molecular Medicine ,Molecule ,Least-Squares Analysis ,Isoxazole ,Selectivity ,IC50 ,HeLa Cells - 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.
- Published
- 2007
- Full Text
- View/download PDF