503026-32-2Relevant academic research and scientific papers
Synthesis and structure-activity relationships of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives as 5-lipoxygenase inhibitors
Bosso, Mira A.,Ezeamuzie, Charles I.,Phillips, Oludotun A.
, p. 1471 - 1482 (2020/07/13)
Oxazolidinone hydroxamic acid derivatives were synthesised and evaluated for inhibitory activity against leukotriene (LT) biosynthesis in three in vitro cell-based test systems and on direct inhibition of recombinant human 5-lipoxygenase (5-LO). Thirteen
Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives
Phillips, Oludotun A.,D'Silva, Roselyn,Bahta, Teklu O.,Sharaf, Leyla H.,Udo, Edet E.,Benov, Ludmil,Eric Walters
, p. 120 - 131 (2015/11/24)
Research activities on the oxazolidinone antibacterial class of compounds continue to focus on developing newer derivatives with improved potency, broad-spectrum activity and safety profiles superior to linezolid. Among the safety concerns with the oxazolidinone antibacterial agents is inhibition of monoamine oxidases (MAO) resulting from their structural similarity with toloxatone, a known MAO inhibitor. Diverse substitution patterns at the C-5 position of the oxazolidinone ring have been shown to significantly affect both antibacterial activity and MAO inhibition to varying degrees. Also, the antibacterial activity of compounds containing iron-chelating functionalities, such as the hydroxamic acids, 8-hydroxyquinolines and catechols have been correlated to their ability to alter iron intake and/or metabolism. Hence a series of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives were synthesized and evaluated for their antibacterial and MAO-A and -B inhibitory activities. The compounds were devoid of significant antibacterial activity but most demonstrated moderate MAO-A and -B inhibitory activities. Computer modeling studies revealed that the lack of potent antibacterial activity was due to significant steric interaction between the hydroxamic acid N-OH oxygen atom and one of the G2540 5′-phosphate oxygen atoms at the bacterial ribosomal binding site. Therefore, the replacement of the 5-acetamidomethyl group of linezolid with the 5-(N-hydroxyacetamido)methyl group present in the hydroxamic acid oxazolidinone derivatives was concluded to be detrimental to antibacterial activity. Furthermore, the 5-(hydroxamic acid)methyl oxazolidinone derivatives were also less active as MAO-A and -B inhibitors compared with linezolid and the selective inhibitors clorgyline and pargyline. In general, the 5-(hydroxamic acid)methyl oxazolidinone derivatives demonstrated moderate but selective MAO-B inhibitory activity.
Synthesis and antibacterial activity of 5-substituted oxazolidinones
Phillips,Udo,Ali,Al-Hassawi
, p. 35 - 41 (2007/10/03)
A series of 5-substituted oxazolidinones with varying substitution at the 5-position of the oxazolidinone ring were synthesized and their in vitro antibacterial activity was evaluated. The compounds demonstrated potent to weak antibacterial activity. A novel compound (PH-027) demonstrated potent antibacterial activity, which is comparable to or better than those of linezolid and vancomycin against antibiotic-susceptible standard and clinically isolated resistant strains of gram-positive bacteria. Although the presence of the C-5-acetamidomethyl functionality at the C-5 position of the oxazolidinones has been widely claimed and reported as a structural requirement for optimal antimicrobial activity in the oxazolidinone class of compounds, our results from this work identified the C-5 triazole substitution as a new structural alternative for potent antibacterial activity in the oxazolidinone class.
