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 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…
Read the paper
Related studies
- Nano Biosensors: Properties, applications and electrochemical techniques
- Electrochemically Synthesized MIP Sensors: Applications in Healthcare Diagnostics
- Toward a Harmonization for Using in situ Nutrient Sensors in the Marine Environment
- Electrochemical determination of rutin by using NiFe2O4 nanoparticles-loaded reduced graphene oxide
- Application of Polyoxometalate-based composites for sensor systems: A review
- Sensitive Electrochemical and Thermal Detection of Human Noroviruses Using Molecularly Imprinted Polymer Nanoparticles Generated against a Viral Target
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.