Electrochemistry/mass spectrometry (EC/MS) for fast generation and identification of novel reactive metabolites of two unsymmetrical bisacridines with anticancer activity.

Agnieszka Potęga; Valentin Göldner; Erik Niehaves; Ewa Paluszkiewicz; Uwe Karst

doi:10.1016/j.jpba.2023.115607

Electrochemistry/mass spectrometry (EC/MS) for fast generation and identification of novel reactive metabolites of two unsymmetrical bisacridines with anticancer activity.

Abstract

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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Authors (5)

Agnieszka Potęga dr hab. inż.
Valentin Göldner
- Uniwersytet w Muenster (Niemcy), Instytut Chemii Nieorganicznej i Analitycznej
Erik Niehaves
- Uniwersytet w Muenster (Niemcy), Instytut Chemii Nieorganicznej i Analitycznej
Ewa Paluszkiewicz dr inż.
Uwe Karst Prof.
- Uniwersytet w Muenster (Niemcy), Instytut Chemii Nieorganicznej i Analitycznej

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artykuły w czasopismach

Published in:

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS no. 235,
ISSN: 0731-7085

Language:

English

Publication year:

2023

Bibliographic description:

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-

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