PhD Scientific Days 2026

Poster Session 3.H - Pharmaceutical Sciences and Health Technologies

Investigation of Oxidative Drug Metabolism with Medium Throughput Biomimetic System

Name of the presenter

Mohácsi, Zsombor Márton

Institute/workplace of the presenter

Department of Pharmaceutical Chemistry

Authors

Mohácsi Zsombor Márton¹, Dr. Decsi Balázs², Dr. Mirzahosseini Arash¹, Dr. Balogh György Tibor¹
1: Semmelweis University, Department of Pharmaceutical Chemistry
2: Budapest University of Technology and Economics, Department of Chemical and Environmental Process Engineering

Text of the abstract

Introduction:
During the early stages of the development of drug candidate molecules information about their metabolic stability is a highly sought after information. However, traditional microsomal studies require a complex reaction mixture with multiple steps, thus it is difficult to analyse the samples taken from the reactions and usually only quantitative results can be obtained. As an alternative method biomimetic techniques are being explored which could provide the adequate results with a simpler one step reaction and without the complex reaction medium, thus enables an easier analysis.
My goals was to explore the biomimetic reactions in detail, by running a medium throughput screening investigation with the biomimetic system to explore which reactions and structures are favoured in the system.
Aims:
In this work the aim is to further investigate the biomimetic system, discover the preferred reaction pathways on different pH levels and reactive substructures and use this information to construct a predicting system which could predict the possible transformations of new chemical structures.
Methods:
The catalyst of the biomimetic system is a synthetic metalloporphyrin, FeTPPS (5,10,15,20-tetrakis(4-sulfonatophenyl) Iron (III) porphyrin), the oxygen donor is tBuOOH and the medium is a 4:1 mixture of methanol and buffer at different pHs (pH=2.7, pH=4.5, pH=6.5, pH=7.4). The reactions were shaken for an hour at 37°C. All samples were directly measured with HPLC-UV-MS and REIMS-HRMS techniques.
Results:
From the 100 compounds examined in the biomimetic system 23 was inert, 25 have shown both biomimetic results and reactions from just tBuOOH and 52 have only shown biomimetic reactions. The reactions have produced 370 metabolites of which we have suggested theoretical structures for 208. The results show that the biomimetic system performs similarly on the lower 2 pH levels (pH=2.7 and 4.5) and drops off at the higher pH levels (pH= 6.5 & 7.4). The prediction system has identified the top performing substructures and can predict the different reaction categories with good certainty.
Conclusion:
The biomimetic system could be used for preliminary screening in drug metabolism and to synthetize specific metabolites. The prediction system can be used to predict future metabolites of previously unknown compounds.
Funding:
SE250+ Phd excellence award 2025/2026/I.