PhD Scientific Days 2025

Poster Session I. - F: Pharmaceutical Sciences and Health Technologies

Biomimetic Oxidative Transformations of Dihydropyridine Derivatives

Name of the presenter

Mohácsi Zsombor Márton

Institute/workplace of the presenter

Department of Pharmaceutical Chemistry

Authors

Zsombor Márton Mohácsi¹, Balázs Csillag¹, Ernák Ferenc Várda², Fekete Zsolt³, András Marton², Arash Mirzahosseini¹, Balázs Decsi², György Tibor Balogh¹, Balázs Volk⁴

1: Department of Pharmaceutical Chemistry
2: Department of Chemical and Environmental Process Engineering
3: Solvo Biotechnology PLC
4: EGIS Pharmaceuticals PLC

Text of the abstract

Introduction:
In the early stage of drug candidate development, information regarding their metabolic stability is greatly desired after. Traditional microsomal studies require complex reaction mixtures, making reaction analysis challenging and typically giving only quantitative results. Biomimetic approaches are being investigated as a possible alternative that may yield favorable outcomes via a simplified one-step reaction, enabling easier analysis. Dihydropyridines are an important class of pharmaceuticals due to their efficacy in managing hypertension, a common disease in modern life. In my prior research, I examined certain members of the dihydropyridine family inside a biomimetic system, which yielded promising results; hence, I intended to analyse the biomimetic reactions of this drug family in greater depth.
Aims:
This work aims to compare the microsomal technique with both a metalloporphyrin based and an electrochemical oxidation system using a library of dihydropyridine derivatives, focusing on the similarity of their product profiles across in the different systems, and the potential of these methods as alternative synthesis routes for metabolites. The major metabolites are isolated for structure elucidation.
Methods:
The main catalyst of the biomimetic system is a synthetic metalloporphyrin, FeTPPS (5,10,15,20-tetrakis(4-sulfonatophenyl) Iron (III) porphyrin), with tBuOOH serving as the oxygen donor and the medium consisting of a 4:1 mixture of methanol and acetate buffer (pH=4.5) solution. The reactions were shaken for an hour at 37°C. The electrochemical reactions were carried out in an electrochemical cell using direct current of 5 mA for 20 minutes, with ammonium-acetate serving as the electrolyte. The microsomal reactions were carried out by Solvo Biotechnology PLC . All samples were processed and directly analysed by HPLC-UV-MS technique.
Results:
The biomimetic system showed very similar results to both the results found in the scientific literature and the microsomal reactions, meanwhile the electrochemical system has produced numerous unique products.
Conclusion:
The biomimetic system may serve for preliminary screening in drug metabolism and for synthesising specific metabolites, meanwhile the electrochemical system is more suited to expand the field of drug candidates.
Funding:
• SE250+ Phd excellence award 2024/2025/I-II.