Electrochemical and in silico approaches for liver metabolic oxidation of antitumor-active triazoloacridinone C -1305 - Publication - Bridge of Knowledge

Your account

login

Search

Electrochemical and in silico approaches for liver metabolic oxidation of antitumor-active triazoloacridinone C -1305

Abstract

5-Dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) is a promising antitumor compound developed in our laboratory. A better understanding of its metabolic transformations is still needed to explain the multidirectional mechanism of pharmacological action of triazoloacridinone derivatives at all. Thus, the aim of the current work was to predict oxidative pathways of C-1305 that would reflect its phase I metabolism. The multi-tool analysis of C-1305 metabolism included electrochemical conversion and in silico sites of metabolism predictions in relation to liver microsomal model. In the framework of the first approach, an electrochemical cell was coupled on-line to an electrospray ionization mass spectrometer. The effluent of the electrochemical cell was also injected onto a liquid chromatography column for the separation of different products formed prior to mass spectrometry analysis. In silico studies were performed using MetaSite software. Standard microsomal incubation was employed as a reference procedure. We found that C-1305 underwent electrochemical oxidation primarily on the dialkylaminoalkylamino moiety. An unknown so far N-dealkylated and hydroxylated C-1305 products have been identified. The electrochemical system was also able to simulate oxygenation reactions. Similar pattern of C-1305 metabolism has been predicted using in silico approach. Both proposed strategies showed high agreement in relation to the generated metabolic products of C-1305. Thus, we concluded that they can be considered as simple alternatives to enzymatic assays, affording time and cost efficiency.

Citations

  • 6

    CrossRef

  • 0

    Web of Science

  • 6

    Scopus

Authors (3)

Cite as

Full text

download paper
downloaded 48 times
Publication version
Accepted or Published Version
License
Creative Commons: CC-BY-NC-ND open in new tab

Keywords

Details

Category:
Articles
Type:
artykuły w czasopismach
Published in:
Journal of Pharmaceutical Analysis no. 10, pages 376 - 384,
ISSN: 2095-1779
Language:
English
Publication year:
2020
Bibliographic description:
Potęga A., Żelaszczyk D., Mazerska Z.: Electrochemical and in silico approaches for liver metabolic oxidation of antitumor-active triazoloacridinone C -1305// Journal of Pharmaceutical Analysis -Vol. 10,iss. 4 (2020), s.376-384
DOI:
Digital Object Identifier (open in new tab) 10.1016/j.jpha.2020.03.011
Verified by:
Gdańsk University of Technology

seen 93 times

Recommended for you

Electrochemical simulation of metabolism for antitumor-active imidazoacridinone C-1311 and in silico prediction of drug metabolic reactions

2019

Electrochemistry meets enzymes: Investigation of the biotransformation pathway of C-1311 based on electrochemical simulation in comparison to in vitro methods.

2014

Phase I and phase II metabolism simulation of antitumor-active 2-hydroxyacridinone with electrochemistry coupled on-line with mass spectrometry.

2019

Electrochemical simulation of enzymatic transformations studied for the selected antitumor acridine derivatives

2014
Meta Tags