title: Evaluation of the monoamine oxidases inhibitory activity of a small series of 5-(azole)methyl oxazolidinones.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. Electronic address: dphillips@hsc.edu.kw.
authors.forename: Oludotun A
authors.initials: OA
authors.lastname: Phillips
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. Electronic address: ls20504@hsc.edu.kw.
authors.forename: Leyla H
authors.initials: LH
authors.lastname: Sharaf
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. Electronic address: jennifer1010@hsc.edu.kw.
authors.forename: Roselyn
authors.initials: R
authors.lastname: D'Silva
authors.affiliation: Department of Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. Electronic address: edet@hsc.edu.kw.
authors.forename: Edet E
authors.initials: EE
authors.lastname: Udo
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. Electronic address: lbenov@hsc.edu.kw.
authors.forename: Ludmil
authors.initials: L
authors.lastname: Benov
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D023303:Oxazolidinones / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D008996:Monoamine Oxidase Inhibitors; D023303:Oxazolidinones; D008995:Monoamine Oxidase
keywords: Antibacterial activity; Gram-positive bacteria; Imidazolyl-oxazolidinone; Monoamine oxidases inhibition; N-substituted-glycinyl oxazolidinone; Triazolyl-oxazolidinone