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

作     者：Agnieszka Potega Dorota Zelaszczyk Zofia Mazerska Agnieszka Pot(e)ga;Dorota (Z)elaszczyk;Zofia Mazerska

作者机构：Department of Pharmaceutical Technology and BiochemistryFaculty of ChemistryGdansk University of TechnologyGabriela Narutowicza St.11/12Gdansk80-233Poland Department of Organic ChemistryFaculty of PharmacyJagiellonian UniversityMedyczna St.9Krakow30-688Poland 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2020年第10卷第4期

页      面：376-384页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100704[医学-药物分析学] 1002[医学-临床医学] 0817[工学-化学工程与技术] 0703[理学-化学] 0702[理学-物理学] 10[医学] 

基　　金：This work was supported by the National Science Center(Poland)(2012/07/D/NZ7/03395) 

主　　题：Antitumor triazoloacridinone P450-catalyzed reactions Electrochemistry/mass spectrometry In silico metabolism Prediction Liver microsomal assay 

摘      要：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 ***,the aim of the current work was to predict oxidative pathways of C-1305 that would reflect its phase I *** multi-tool analysis of C-1305 metabolism included electrochemical conversion and in silico sites of metabolism predictions in relation to liver microsomal *** the framework of the first approach,an electrochemical cell was coupled on-line to an electrospray ionization mass *** effluent of the electrochemical cell was also injected onto a liquid chromatography column for the separation of different products formed prior to mass spectrometry *** silico studies were performed using MetaSite *** microsomal incubation was employed as a reference *** found that C-1305 underwent electrochemical oxidation primarily on the dialkylaminoalkylamino *** unknown N-dealkylated and hydroxylated C-1305 products have been *** electrochemical system was also able to simulate oxygenation *** pattern of C-1305 metabolism has been predicted using in silico *** proposed strategies showed high agreement in relation to the generated metabolic products of ***,we conclude that they can be considered as simple alternatives to enzymatic assays,affording time and cost efficiency.