Synthesis and antibacterial activity of pyrroloaryl-substituted oxazolidinones

Paget, Steven D.; Foleno, Barbara D.; Boggs, Christine M.; Goldschmidt, Raúl; Hlasta, Dennis J.; Weidner‐Wells, Michele A.; Werblood, Harvey M.; Wira, Ellyn; Bush, Karen; Macielag, Mark J.

doi:10.1016/j.bmcl.2003.08.031

Cited by 39 publications

(15 citation statements)

References 11 publications

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“…The development of new oxazolidinone compounds as antibacterials (6,16,18,19,29,31,37,38) and as monoamine oxidase A inhibitors (13,27) remains an active area of research involving several companies. However, since the results of the study reported here indicate that oxazolidinones that are highly potent as antibacterials are likely to be potent inhibitors of mitochondrial protein synthesis and may display increased toxicity in animals, a strong case can be made for evaluating the effects on mitochondria during the development of drugs of the oxazolidinone class.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Mammalian Mitochondrial Protein Synthesis by Oxazolidinones

McKee

Ferguson

Bentley

et al. 2006

Antimicrob Agents Chemother

240

182

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The effects of a variety of oxazolidinones, with different antibacterial potencies, including linezolid, on mitochondrial protein synthesis were determined in intact mitochondria isolated from rat heart and liver and rabbit heart and bone marrow. The results demonstrate that a general feature of the oxazolidinone class of antibiotics is the inhibition of mammalian mitochondrial protein synthesis. Inhibition was similar in mitochondria from all tissues studied. Further, oxazolidinones that were very potent as antibiotics were uniformly potent in inhibiting mitochondrial protein synthesis. These results were compared to the inhibitory profiles of other antibiotics that function by inhibiting bacterial protein synthesis. Of these, chloramphenicol and tetracycline were significant inhibitors of mammalian mitochondrial protein synthesis while the macrolides, lincosamides, and aminoglycosides were not. Development of future antibiotics from the oxazolidinone class will have to evaluate potential mitochondrial toxicity.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Mammalian Mitochondrial Protein Synthesis by Oxazolidinones

McKee

Ferguson

Bentley

et al. 2006

Antimicrob Agents Chemother

240

182

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“…The conversion of isoindolines to isoindoles has been performed by means of conventional oxidants, such as DDQ, 43 MnO 2 44 and m-CPBA, 45 resulting in aromatisation of the respective precursors. The synthesis of indole (84, Scheme 18), pyridine (86, Scheme 19), pyrimidine (88, Scheme 19) and quinolinone (90, Scheme 20) containing isoindole analogues has been reported by this methodology.…”

Section: Oxidative Processesmentioning

confidence: 99%

Synthesis of isoindoles and related iso-condensed heteroaromatic pyrroles

2012

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Over the past few years, isoindoles have found wide application in materials science. Isoindole containing BODIPY dyes are highly fluorescent materials and have been extensively used in various fields of science. Phthalocyanines, metal containing cyclic tetramers of isoindole, form coordination complexes with most elements of the periodic table. These complexes are intensely coloured and are used as pigments and dyes. However, isoindoles are relatively unstable 10π-heteroaromatic systems and few synthetic methods provide these compounds in good yields. This tutorial review will give an overview of the reported synthetic methods towards isoindoles and related heteroaromatic systems over a time span of approximately 10 years (2000 to current), including the applications where they have been reported. The importance of the field will be illustrated and factors influencing product stability will be discussed.

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“…Our interest in pyridine based oxazolidinones is due to their potential for metal chelation and possible use in therapeutics. [28][29][30][31][32][33][34] In our attempt to generate a pyridine based oxazolidinone, we synthesized 3-(pyridin-2-ylmethyl)oxazolidin-2-one (L) in the presence of SOCl 2 (Scheme 2) using air (atmospheric CO 2 ) and without any added base. L is also a potential metal binder and hence, three metal complexes of the formulae [Cu(L) 2 (ClO 4 ) 2 ] (1), trans-[Pt(L)(DMSO)Cl 2 ] (2), and trans-[Pd(L) 2 Cl 2 ] (3) were synthesized, to probe the potential of the newly designed pyridyl oxazolidinone ligand.…”

Section: Introductionmentioning

confidence: 99%