Linezolid and Its Immunomodulatory Effect: In Vitro and In Vivo Evidence

Wang, Jin; Xia, Lei; Wang, Rui; Cai, Yun

doi:10.3389/fphar.2019.01389

Cited by 11 publications

(14 citation statements)

References 47 publications

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“…Oxazolidinones (1), five-membered heterocyclic rings containing an ester group adjacent to a nitrogen atom, are important compounds in synthetic and pharmaceutical chemistry because of their considerable use as antibiotics [1], immunomodulators [2], antibacterials [3], as well as synthetic intermediates and chiral auxiliaries for various organic conversions [4][5][6][7]. Linezolid [1][2][3] (3) and cytoxazone [8,9] (4) are oxazolidinone derivatives having significant biological activities. Linezolid 3is the first oxazolidinone drug approved in 2000 by the Food and Drug Administration (FDA) for the treatment of multidrug resistant Gram-positive bacterial infections (Scheme 1) [10].…”

Section: Introductionmentioning

confidence: 99%

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One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

Demir¹,

Sarı²,

Çetinkaya³

et al. 2020

Beilstein J. Org. Chem.

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The one-pot reaction of chlorosulfonyl isocyanate (CSI) with epoxides having phenyl, benzyl and fused cyclic alkyl groups in different solvents under mild reaction conditions without additives and catalysts was studied. Oxazolidinones and five-membered cyclic carbonates were obtained in ratios close to 1:1 in the cyclization reactions. The best yields of these compounds were obtained in dichloromethane (DCM). Together with 16 known compounds, two novel oxazolidinone derivatives and two novel cyclic carbonates were synthesized with an efficient and straightforward method. Compared to the existing methods, the synthetic approach presented here provides the following distinct advantageous: being a one-pot reaction with metal-free reagent, having shorter reaction times, good yields and a very simple purification method. Moreover, using the density functional theory (DFT) method at the M06-2X/6-31+G(d,p) level of theory the mechanism of the cycloaddition reactions has been elucidated. The further investigation of the potential energy surfaces associated with two possible channels leading to oxazolidinones and five-membered cyclic carbonates disclosed that the cycloaddition reaction proceeds via an asynchronous concerted mechanism in gas phase and in DCM.

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Section: Introductionmentioning

confidence: 99%

“…Five-membered cyclic carbonate (1,3-dioxolan-2-one) (2) and its derivatives are valuable synthetic targets on account of several applications and pertinent properties. They are found in various natural and potential pharmaceutical products [15].…”

Section: Introductionmentioning

confidence: 99%

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

Demir¹,

Sarı²,

Çetinkaya³

et al. 2020

Beilstein J. Org. Chem.

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show abstract

“…Oxazolidinones (1), five-membered heterocyclic rings containing nitrogen atom and ester group, are important compounds in organic chemistry and pharmaceutical chemistry because of their considerable interest as antibiotics [1], immunomodulatories [2], antibacterials [3], as well as synthetic intermediates and chiral auxiliaries for various organic conversions [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Linezolid [1][2][3] (3) and cytoxazone [8,9] resistant Enterococcus faecalis (VRE) (Scheme 1) [10]. Tedizolid phosphate (trade name Sivextro) is another oxazolidinone-class antibiotic being more potent against enterococci and staphylococci when compared with Linezolid [11].…”

Section: Introductionmentioning

confidence: 99%

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One-Pot Synthesis of Oxazolidinones and Five-Membered Cyclic Carbonates from Epoxides and Chlorosulfonyl isocyanate: Theoretical Evidence for the Asynchronous Concerted Pathway

Demir¹,

Sarı²,

Çetinkaya³

et al. 2020

Preprint

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The one-pot reaction of chlorosulfonyl isocyanate (CSI) with epoxides having substituted phenyl, benzyl and fused cyclic alkyl groups in different solvents under mild reaction conditions without additives and catalysts was studied. Oxazolidinones and five-membered cyclic carbonates were obtained with a ratio close to (1:1) in the cyclization reactions. The best reaction conversion for the synthesis of these compounds was carried out in dichloromethane (DCM). The method presented here has distinct advantageous over the existing methods such as one-pot reaction, shorter reaction times, metal-free reagent, good yields and very simple purification method. The mechanism for the cycloaddition reactions has been elucidated using density functional theory (DFT) method at the M06-2X/6-31+G(d,p) level. The investigation of the potential energy surfaces associated with two possible channels leading to oxazolidinones and five-membered cyclic carbonates revealed that the cycloaddition reaction takes place through an asynchronous concerted mechanism in gas phase and in DCM.

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Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?

Dalhoff

2020

Infection

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Background Selective toxicity antibacteribiotics is considered to be due to interactions with targets either being unique to bacteria or being characterized by a dichotomy between pro- and eukaryotic pathways with high affinities of agents to bacterial- rather than eukaryotic targets. However, the theory of selective toxicity oversimplifies the complex modes of action of antibiotics in pro- and eukaryotes. Methods and objective This review summarizes data describing multiple modes of action of antibiotics in eukaryotes. Results Aminoglycosides, macrolides, oxazolidinones, chloramphenicol, clindamycin, tetracyclines, glycylcyclines, fluoroquinolones, rifampicin, bedaquillin, ß-lactams inhibited mitochondrial translation either due to binding to mitosomes, inhibition of mitochondrial RNA-polymerase-, topoisomerase 2ß-, ATP-synthesis, transporter activities. Oxazolidinones, tetracyclines, vancomycin, ß-lactams, bacitracin, isoniazid, nitroxoline inhibited matrix-metalloproteinases (MMP) due to chelation with zinc and calcium, whereas fluoroquinols fluoroquinolones and chloramphenicol chelated with these cations, too, but increased MMP activities. MMP-inhibition supported clinical efficacies of ß-lactams and daptomycin in skin-infections, and of macrolides, tetracyclines in respiratory-diseases. Chelation may have contributed to neuroprotection by ß-lactams and fluoroquinolones. Aminoglycosides, macrolides, chloramphenicol, oxazolidins oxazolidinones, tetracyclines caused read-through of premature stop codons. Several additional targets for antibiotics in human cells have been identified like interaction of fluoroquinolones with DNA damage repair in eukaryotes, or inhibition of mucin overproduction by oxazolidinones. Conclusion The effects of antibiotics on eukaryotes are due to identical mechanisms as their antibacterial activities because of structural and functional homologies of pro- and eukaryotic targets, so that the effects of antibiotics on mammals are integral parts of their overall mechanisms of action.

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Linezolid and Its Immunomodulatory Effect: In Vitro and In Vivo Evidence

Cited by 11 publications

References 47 publications

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

One-Pot Synthesis of Oxazolidinones and Five-Membered Cyclic Carbonates from Epoxides and Chlorosulfonyl isocyanate: Theoretical Evidence for the Asynchronous Concerted Pathway

Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?

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