| Autor: |
Matos IA; Department of Chemistry, Graduate Program in Chemistry, Federal University of Sergipe-UFS, São Cristóvão-SE, Brazil., Goes Pinto AC; Department of Chemistry, Graduate Program in Chemistry, Federal University of Sergipe-UFS, São Cristóvão-SE, Brazil., Ferraz MVF; Aggeu Magalhães Institute, Recife-PE, Brazil., Adan WCS; Department of Pharmaceutical Sciences, Postgraduate Program in Pharmaceutical Sciences, Federal University of Espírito Santo-UFES, Vitória-ES, Brazil., Rodrigues RP; Department of Pharmacy, Graduate Program in Chemistry, Federal University of Sergipe-UFS, São Cristóvão-SE, Brazil., Dos Santos JX; Department of Chemistry, Graduate Program in Chemistry, Federal University of Sergipe-UFS, São Cristóvão-SE, Brazil., Kitagawa RR; Department of Pharmaceutical Sciences, Postgraduate Program in Pharmaceutical Sciences, Federal University of Espírito Santo-UFES, Vitória-ES, Brazil., Lins RD; Aggeu Magalhães Institute, Recife-PE, Brazil., Oliveira TB; Department of Pharmacy, Graduate Program in Chemistry, Federal University of Sergipe-UFS, São Cristóvão-SE, Brazil., Costa Junior NBD; Department of Chemistry, Graduate Program in Chemistry, Federal University of Sergipe-UFS, São Cristóvão-SE, Brazil. |
| Abstrakt: |
Herein we describe the use of molecular docking simulations, quantitative structure-activity relationships studies and ADMETox predictions to analyse the molecular recognition of a series of 7-aryl-2,4-diaminoquinazoline derivatives on the inhibition of Staphylococcus aureus dihydrofolate reductase and conducted a virtual screening to discover new potential inhibitors. A quantitative structure-activity relationship model was developed using 40 compounds and two selected descriptors. These descriptors indicated the importance of pKa and molar refractivity for the inhibitory activity against Sa DHFR. The values of R 2 train , CV LOO and R 2 test generated by the model were 0.808, 0.766, and 0.785, respectively. The integration between QSAR, molecular docking, ADMETox analysis and molecular dynamics simulations with binding free energies calculation, yielded the compounds PC-124127620, PC-124127795 and PC-124127805 as promising candidates to Sa DHFR inhibitors. These compounds presented high potency, good pharmacokinetics and toxicological profile. Thus, these molecules are good potential antimicrobial agent to treatment of infect disease caused by S. aureus .Communicated by Ramaswamy H. Sarma. |
