Oxydationsprodukte von Thiocarbonsäureamiden, III. Oxydationsprodukte primärer Thioamide

Walter, Wolfgang; Curts, Julius

doi:10.1002/cber.19600930710

Cited by 42 publications

(4 citation statements)

References 4 publications

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“…Unlabeled ETA synthesized by using the same procedure cochromatographed with commercially available ETA (Sigma-Aldrich) and showed the correct analytical data. Metabolites were identified by comparison with wellcharacterized synthetic standards prepared as follows: the sulfoxide (2) was prepared by hydrogen peroxide oxidation of ETA as described (29 Cells from sequential culture aliquots from the metabolic conversion assays (volumes given in figure legends) were collected by filtration onto 0.22-m GS filter disks (Millipore) under vacuum on a Hoeffer apparatus and were washed twice with 0.1 mM sodium phosphate (pH 7.5), 100 mM NaCl (500 l). The cell-associated radioactivity was measured in 4 ml of EcoscintA scintillation solution (National Diagnostics).…”

Section: Experimental Procedures Synthesis Of 2-ethyl-[ 14 C]thioisonmentioning

confidence: 99%

Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis

DeBarber

Mdluli

Bosman

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

310

335

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Ethionamide (ETA) is an important component of second-line therapy for the treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled ETA and an examination of drug metabolites formed by whole cells of Mycobacterium tuberculosis (MTb) have allowed us to demonstrate that ETA is activated by Soxidation before interacting with its cellular target. ETA is metabolized by MTb to a 4-pyridylmethanol product remarkably similar in structure to that formed by the activation of isoniazid by the catalase-peroxidase KatG. We have demonstrated that overproduction of Rv3855 (EtaR), a putative regulatory protein from MTb, confers ETA resistance whereas overproduction of an adjacent, clustered monooxygenase (Rv3854c, EtaA) confers ETA hypersensitivity. Production of EtaA appears to be negatively regulated by EtaR and correlates directly with [ 14 C]ETA metabolism, suggesting that EtaA is the activating enzyme responsible for thioamide oxidation and subsequent toxicity. Coding sequence mutations in EtaA were found in 11 of 11 multidrug-resistant MTb patient isolates from Cape Town, South Africa. These isolates showed broad cross-resistance to thiocarbonyl containing drugs including ETA, thiacetazone, and thiocarlide.

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Section: Experimental Procedures Synthesis Of 2-ethyl-[ 14 C]thioisonmentioning

confidence: 99%

Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis

DeBarber

Mdluli

Bosman

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

310

335

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“…Their oxidation is governed largely by the intrinsic chemistry of the thiocarbonyl group and its soft, highly polarizable, and easily oxidized sulfur atom (Scheme 1) (12). Thioamide S-oxides such as 2 were first prepared and characterized by Walter in the 1950s (17), and in many cases, they are relatively stable structures. S-Oxide metabolites of TA, TB, and ETH have been isolated, but their further S-oxidation generates S,S-dioxides (e.g., 3) that are extremely reactive and not isolable as such.…”

Section: Introductionmentioning

confidence: 99%

Covalent Modification of Microsomal Lipids by Thiobenzamide Metabolites in Vivo

Ikehata

Koen

et al. 2007

Chem. Res. Toxicol.

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Thiobenzamide (TB) is hepatotoxic in rats causing centrolobular necrosis, steatosis, cholestasis, and hyperbilirubinemia. It serves as a model compound for a number of thiocarbonyl compounds that undergo oxidative bioactivation to chemically reactive metabolites. The hepatotoxicity of TB is strongly dependent on the electronic character of substituents in the meta- and para-positions, with Hammett rho values ranging from -4 to -2. On the other hand, ortho substituents that hinder nucleophilic addition to the benzylic carbon of S-oxidized TB metabolites abrogate the toxicity and protein covalent binding of TB. This strong linkage between the chemistry of TB and its metabolites and their toxicity suggests that this model is a good one for probing the overall mechanism of chemically induced biological responses. While investigating the protein covalent binding of TB metabolites, we noticed an unusually large amount of radioactivity associated with the lipid fraction of rat liver microsomes. Thin-layer chromatography showed that most of the radioactivity was contained in a single spot more polar than the neutral lipids but less polar than the phospholipid fractions. Mass spectral analyses aided by the use of synthetic standards identified the material as N-benzimidoyl derivatives of typical microsomal phosphatidylethanolamine (PE) lipids. Quantitative analysis indicated that up to 25% of total microsomal PE became modified within 5 h after a hepatotoxic dose of TB. Further studies will be required to determine the contribution of lipid modification to the hepatotoxicity of TB.

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“…This reaction involves two types of monomers: 1,4-bis(2,4,5-triphenylcyclopentadienone)benzene or its sulfonates, and di(ethynyl)benzene or its derivatives (Figure 6A). 56,[79][80][81] During the reaction, 1,4-bis(2,4,5-triphenylcyclopentadienone)benzene eliminates the carbonyl group and undergoes in situ ring formation, resulting in the formation of phenyl groups. The precise structure of these polymers remains uncertain due to two factors.…”

Section: General Synthesis Strategiesmentioning

confidence: 99%

All‐carbon backbone aromatic polymers for proton exchange membranes

Li,

Chai,

Liu

et al. 2023

Journal of Polymer Science

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Proton exchange membranes (PEMs) play a crucial role in energy storage and conversion technologies such as fuel cells, redox flow batteries, and water electrolysis. Currently, perfluorosulfonic acid polymer (PFSA) membranes are the most commonly used PEM materials. However, PFSA membranes possess certain drawbacks, including the high dependence of proton conductivity on humidity, low glass transition temperatures, and complex synthesis processes. In recent decades, significant efforts have been dedicated to developing various alternative PEM materials, such as the sulfonated products of polyether ether ketone, poly(phenylene oxide), polysulfone, and polyimide. However, the backbones of these polymers often contain heteroatoms that are prone to breaking under practical working conditions, leading to reduced chemical stability. In contrast, all‐carbon backbone aromatic polymers exhibit excellent chemical stability, thermal stability, and mechanical properties, as well as high proton conductivity upon incorporating suitable acidic groups, which makes them promising alternatives for PEM materials. This review aims to summarize the recent research progress about all‐carbon backbone aromatic polymers, with a specific focus on synthesis strategies, structure–performance relationships, and applications in PEMs.

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Oxydationsprodukte von Thiocarbonsäureamiden, III. Oxydationsprodukte primärer Thioamide

Abstract: Es wird über die Synthese einer Anzahl von Thioamid‐S‐oxyden der Formel berichtet. Unter den neu dargestellten Verbindungen befindet sich das erste Glied dieser Reihe, das Thioformamid‐S‐oxyd.

Cited by 42 publications

References 4 publications

Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis

Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis

Covalent Modification of Microsomal Lipids by Thiobenzamide Metabolites in Vivo

All‐carbon backbone aromatic polymers for proton exchange membranes

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