RESUMO
New substituted imidazolidinone sulfonamides have been developed using a rational drug design strategy. Predictive QSAR models for the search of new antibacterials were created using the OCHEM platform. Regression models were applied to verify a virtual chemical library of new imidazolidinone derivatives designed to have antibacterial activity. A number of substituted imidazolidinone sulfonamides as effective antibacterial agents were identified by QSAR prediction, synthesized and characterized by spectral and elemental, and tested inâ vitro. Six studied compounds have shown the highest inâ vitro antibacterial activity against Gram-negative E. coli and Gram-positive S. aureus multidrug-resistant strains. The inâ vivo acute toxicity of these imidazolidinone sulfonamides based on the LC50 value ranged from 16.01 to 44.35â mg/L (slightly toxic compounds class). The results of molecular docking suggest that the antibacterial mechanism of the compounds can be associated with the inhibition of post-translational modification processes of bacterial peptides and proteins.
Assuntos
Antibacterianos , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Simulação de Acoplamento Molecular , Sulfonamidas/farmacologia , Sulfonamidas/química , Escherichia coli , Sulfanilamida , Testes de Sensibilidade MicrobianaRESUMO
A new fluorinated azidoethaneâ1-azido-1,1,2,2-tetrafluoroethaneâwas prepared in quantitative yield by the addition of an azide anion to tetrafluoroethylene in a protic medium. The title azide was shown to be thermally stable and insensitive to impact. Copper(I)-catalyzed [3 + 2] cycloaddition with alkynes afforded 4-substituted N-tetrafluoroethyl-1,2,3-triazoles which underwent rhodium(II)-catalyzed transannulation with nitriles to novel N-tetrafluoroethylimidazoles or the reaction with triflic acid to enamido triflates. [3 + 2] Cycloaddition of the title azide with primary amines afforded novel 5-difluoromethyl tetrazoles.