Conversion of the thiocarbonyl group into the carbonyl group

Corsaro, Antonino; Pistarà, Venerando

doi:10.1016/s0040-4020(98)00880-1

Cited by 96 publications

(40 citation statements)

References 194 publications

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“…4a, inset). This latter compound is formed through the oxidation of the thiocarbonyl group of Bp4eT and is in line with the direct oxidation of the thiocarbonyl moiety that has been described using different conditions [28].…”

Section: Resultssupporting

confidence: 65%

LC-MS/MS identification of the principal in vitro and in vivo phase I metabolites of the novel thiosemicarbazone anti-cancer drug, Bp4eT

et al. 2012

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The iron chelator, 2-benzoylpyridine-4-ethyl-3-thiosemicarbazone (Bp4eT), was identified as a lead compound of the 2-benzoylpyridine thiosemicarbazone series, which were designed as potential anti-cancer agents. This ligand has been shown to possess potent anti-proliferative activity with a highly selective mechanism of action. However, further progress in the development of this compound requires data regarding its metabolism in mammals. The aim of this study was to identify the main in vitro and in vivo phase I metabolites of Bp4eT using liquid chromatography tandem mass spectrometry (LC-MS/MS). Two metabolites were detected after incubation of this drug with rat and human liver microsomal fractions. Based on LC-MS(n) analysis, the metabolites were demonstrated to be 2-benzoylpyridine-4-ethyl-3-semicarbazone and N (3)-ethyl-N (1)-[phenyl(pyridin-2-yl)methylene]formamidrazone, with both resulting from the oxidation of the thiocarbonyl group. The identity of these metabolites was further shown by LC-MS/MS analysis of these latter compounds which were prepared by oxidation of Bp4eT with hydrogen peroxide and their structures confirmed by nuclear magnetic resonance and infrared spectra. Both the semicarbazone and the amidrazone metabolites were detected in plasma, urine, and feces after i.v. administration of Bp4eT to rats. In addition, another metabolite that could correspond to hydroxylated amidrazone was found in vivo. Thus, oxidative pathways play a major role in the phase I metabolism of this promising anti-tumor agent. The outcomes of this study will be further utilized for: (1) the development and validation of the analytical method for the quantification of Bp4eT and its metabolites in biological materials; (2) to design pharmacokinetic experiments; and to (3) evaluate the potential contribution of the individual metabolites to the pharmacodynamics/toxico-dynamics of this novel anti-proliferative agent.

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Section: Resultssupporting

confidence: 65%

LC-MS/MS identification of the principal in vitro and in vivo phase I metabolites of the novel thiosemicarbazone anti-cancer drug, Bp4eT

et al. 2012

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“…4D). According to the literature, this finding may be explained by hydrogen peroxideinduced conversion of the thiocarbonyl to carbonyl group of the chelator [41]. Besides the main oxidative product, the synthetic precursor 2,2 -dipyridylketone was also detected in the exposed samples (Fig.…”

Section: Dp44mtmentioning

confidence: 59%

Development and validation of HPLC-DAD methods for the analysis of two novel iron chelators with potent anti-cancer activity

Mrkvičková

Kovařı́ková

Klimeš

et al. 2007

Journal of Pharmaceutical and Biomedical Analysis

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“…The conversion of thioureas into ureas has attracted the interest of chemists since long (46). The conversion of toxic thiourea to biologically benign urea can be achieved by both biological as well as chemical oxidants including dioxygen (47).…”

Section: Oxidation Of Thiourea To Ureamentioning

confidence: 99%

“…Potassium peroxodisulfate is known to degrade diphenylthiourea under strongly basic conditions to a mixture of the corresponding urea, sulfur, and phenyl isothiocyanate (46,113). Silver, mercury, and lead oxides in water at room temperature eliminate hydrogen sulfide from the thiourea molecule giving cyanamide (114 (115).…”

Section: Oxidative Degradationmentioning

confidence: 99%