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 in vitro. Six studied compounds have shown the highest in vitro antibacterial activity against Gram-negative E. coli and Gram-positive S. aureus multidrug-resistant strains. The in vivo acute toxicity of these imidazolidinone sulfonamides based on the LC50 value ranged from 16.01 to 44.35 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.
Keywords: QSAR; antibacterial activity; imidazolidinone sulphonamides; molecular docking; toxicity.
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