Oxazolidinone class of compounds continue to generate interest as promising agents effective against sensitive and resistant Gram-positive pathogenic bacteria strains. Recent focus is to develop new potent derivatives with improved broad-spectrum activity and safety profile superior to linezolid. An important toxicity issue for this class of compounds arises from the structural similarity with toloxatone, a known MAO inhibitor. Herein, we report the evaluation of a small series of 5-(1H-1,2,3-triazolyl)-, 5-(4-methyl-1H-1,2,3-triazolyl)-, 5-(5-methyl-1H-1,2,3-triazolyl)- and 5-imidazolyl-methyl oxazolidinone analogs with and without antibacterial activity for their effects as inhibitors of monoamine-A and -B (MAO-A and -B) oxidases. Substitutions at the oxazolidinone C-5 position significantly affected antibacterial activity and MAO inhibition. The N-substituted-glycinyl 1H-1,2,3-triazolyl methyl oxazolidinones with potent antibacterial activity demonstrated only weak to moderate affinity for MAO-A and -B, supporting further investigation for this group of compounds.
Keywords: Antibacterial activity; Gram-positive bacteria; Imidazolyl-oxazolidinone; Monoamine oxidases inhibition; N-substituted-glycinyl oxazolidinone; Triazolyl-oxazolidinone.
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