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Electrochemistry/mass spectrometry (EC/MS) for fast generation and identification of novel reactive metabolites of two unsymmetrical bisacridines with anticancer activity.
Abstrakt
The development of a new drug requires knowledge about its metabolic fate in a living organism, regarding the comprehensive assessment of both drug therapeutic activity and toxicity profiles. Electrochemistry (EC) coupled with mass spectrometry (MS) is an efficient tool for predicting the phase I metabolism of redox-sensitive drugs. In particular, EC/MS represents a clear advantage for the generation of reactive drug transformation products and their direct identification compared to biological matrices. In this work, we focused on the characterization of novel electrochemical products of two representative unsymmetrical bisacridines (C-2028 and C-2045) with demonstrated high anticancer activity. The electrochemical thin-layer flow-through cell μ-PrepCell 2.0 (Antec Scientific) was used here for the effective metabolite electrosynthesis. The electrochemical simulation of C-2028 reductive and C-2045 oxidative metabolism resulted in the generation of new products that were not observed before. The formation of nitroso [M-O+H]+ and azoxy [2M-3O+H]+ species from C-2028, as well as a series of hydroxylated and/or dehydrogenated products, including possible quinones [M-2H+H]+ and [M+O-2H+H]+ from C-2045, was demonstrated. For the latter, a glutathione S-conjugate (m/z 935.3130) was also obtained in measurements supplemented with the excess of reduced glutathione. For the identification of the products of interest, structural confirmation based on MS/MS fragmentation experiments was performed. Novel products of electrochemical conversions of unsymmetrical bisacridines were discussed in the context of their possible biological effect on the human organism.
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Autorzy (5)
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Valentin Göldner
- Uniwersytet w Muenster (Niemcy), Instytut Chemii Nieorganicznej i Analitycznej
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Erik Niehaves
- Uniwersytet w Muenster (Niemcy), Instytut Chemii Nieorganicznej i Analitycznej
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Uwe Karst Prof.
- Uniwersytet w Muenster (Niemcy), Instytut Chemii Nieorganicznej i Analitycznej
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Informacje szczegółowe
- Kategoria:
- Publikacja w czasopiśmie
- Typ:
- artykuły w czasopismach
- Opublikowano w:
-
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
nr 235,
ISSN: 0731-7085 - Język:
- angielski
- Rok wydania:
- 2023
- Opis bibliograficzny:
- Potęga A., Göldner V., Niehaves E., Paluszkiewicz E., Karst U.: Electrochemistry/mass spectrometry (EC/MS) for fast generation and identification of novel reactive metabolites of two unsymmetrical bisacridines with anticancer activity.// JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS -Vol. 235,iss. - (2023), s.115607-
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1016/j.jpba.2023.115607
- Źródła finansowania:
-
- COST_FREE
- Weryfikacja:
- Politechnika Gdańska
wyświetlono 41 razy
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