Exploring the structure–activity relationship of oxazolidinones as HIV-1 protease inhibitors—QSAR and pharmacophore modelling studies
| Autor: | Veerasamy Ravichandran, Krishnamoorthy Venkateskumar, S. Shalini, Rajak Harish |
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| Rok vydání: | 2016 |
| Předmět: |
Steric effects
Quantitative structure–activity relationship Protease biology 010405 organic chemistry Chemistry Stereochemistry Hydrogen bond Process Chemistry and Technology medicine.medical_treatment 01 natural sciences Combinatorial chemistry 0104 chemical sciences Computer Science Applications Analytical Chemistry 010404 medicinal & biomolecular chemistry HIV-1 protease biology.protein medicine Structure–activity relationship Pharmacophore Spectroscopy Software Applicability domain |
| Zdroj: | Chemometrics and Intelligent Laboratory Systems. 154:52-61 |
| ISSN: | 0169-7439 |
| DOI: | 10.1016/j.chemolab.2016.03.017 |
| Popis: | In the present study, 2D QSAR and 3D QSAR models and pharmacophore hypothesis were evaluated for a series of N-aryl-oxazolidinone-5-carboxamides to predict their HIV-1 protease inhibitory activity. The developed QSAR models were validated by external validation method, leave-one-out and leave-many-outcross validation, Y-randomization method and applicability domain analysis. The primary findings of this study were that the number of carbon atoms separated from any specific carbon atom by 2- and 7-bond distances, and the number of fluorine atoms separated from any specific fluorine atom by a 5-bond distance in a molecule, altered the compounds' inhibitory action on HIV-1 protease. Further, 3D QSAR study results indicated that the presence of electrostatic and steric field descriptors in N-aryl-oxazolidinone-5-carboxamides significantly inhibited HIV-1 protease. The generated pharmacophore hypothesis of the compounds indicated the significance of the two aromatic and three hydrogen bond acceptor features on HIV-1 protease's inhibitory activity. The proposed model also provided a better understanding of HIV-1 protease's inhibitory activity on oxazolidinones and could be used as guidance for the proposition of new anti-HIV agents. |
| Databáze: | OpenAIRE |
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