Institute for Pharmacy
Pharmaceutical and Medicinal Chemistry

New medicinal compounds

By utilizing 3D models of receptors and active compounds, we successfully identify new lead structures for further drug development. We combine in silico screening with in vitro experiments to efficiently discover active substances. In our ongoing projects, we have identified dopamine receptor ligands and characterized their selectivity, discovered β-tubulin-binding compounds, and, in collaboration with synthetic chemists, helped advance the development of two compound groups: anti-inflammatory diflapolin derivatives and dihydrochalcones, which exhibit a broad spectrum of activity.

Physicochemical properties of test compounds

New drug candidates must not only demonstrate strong receptor binding but also possess suitable physicochemical properties to be viable as medications. In addition to computational calculation of these properties, we developing in vitro test systems that can evaluate and account for them. Current experimental methods for measuring logP values are complemented by an ongoing project focusing on the use of solubilizers in cell-based in vitro tests. Other key properties, such as compound stability in solution and human plasma, are also examined in our projects.

Chemical side effects

Everyday, ee are exposed to various chemicals, such as those found in cleaning products, cosmetics, pharmaceuticals, plastics, and food additives. Many of these chemicals can be detected in human blood or urine, making it crucial to investigate the potential health risks they pose. As part of the EU REACH program and the US National Toxicity Program, chemicals are assessed for their hormonal effects. At the same time, researchers are exploring meaningful alternatives (in silico/in vitro) to animal testing.

Computer-based predictions play a vital role in prioritizing chemicals for in vitro/in vivo testing, helping to identify those chemicals most likely to exhibit biological effects and prioritizing them for testing. Pharmacophore models serve as excellent in silico screening tools to filter out potentially active substances from large chemical databases. Recently, we contributed to the identification of drug compounds that could potentially trigger hypertension.

Lipid Droplets (LDs) in aging and inflammation

Our research on human lipid metabolism aims to lay the groundwork for improved treatments for common diseases associated with obesity. Lipids serve multiple functions in cellular energy metabolism, are key components of cell membranes, and play a vital role in cellular communication, as well as the initiation and resolution of inflammatory processes. However, free fatty acids are cytotoxic and can damage the structure and function of biological membranes. In cells, free fatty acids are metabolized into complex and neutral lipids to protect against toxic effects (lipotoxicity), with neutral lipids being stored in LDs. Chemicals, pharmaceuticals, and hypercaloric diets can promote the storage of fat and increase the number and size of LDs. Excessive LD accumulation in liver cells, however, can contribute to the progression of chronic diseases such as metabolic-associated fatty liver disease (MAFLD, also known as non-alcoholic fatty liver disease (NAFLD)) and cancer. We characterize the serum lipidomes of different MAFLD patient cohorts to define individualized therapeutic options.

LDs consist of a core of neutral lipids (triacylglycerols and cholesterol esters) surrounded by a single layer of phospholipids. Embedded in this phospholipid layer are specific proteins involved in lipid metabolism. Inflammation, aging, and related diseases such as cancer are multifactorial processes in which damaged proteins and lipids accumulate intracellularly. To maintain cellular homeostasis, various organelle-specific systems have evolved to degrade damaged molecules, and these systems are closely interconnected. Our research suggests that under high stress conditions, LDs can act as a backup system.

As highly dynamic organelles, LDs serve as a hub for the transfer of toxic lipids and proteins, as they can directly interact with various cellular organelles (lysosomes, peroxisomes, mitochondria, nucleus, and ER). We primarily address these questions using modern mass spectrometry methods. The statistical analysis of the resulting complex datasets is aimed at efficiently translating our basic research findings into potential clinical applications.

The amaZon Speed ETD Mass Spectrometer by Bruker is a state-of-the-art ion trap mass spectrometer. Its advanced ion trap mass analyzer offers fast scan speeds while maintaining high mass accuracy and sensitivity. Additionally, fragmentation experiments can be performed to improve selectivity during analysis and to provide detailed structural information about analyte molecules.

The built-in ESI ion source allows for both direct injection and coupling with High-Performance Liquid Chromatography (HPLC). These features make the amaZon mass spectrometer versatile, suitable for a wide range of applications—from the structural identification of unknown analytes to metabolomics and proteomics studies.

The latest-generation GC/MS is equipped with a turbomolecular pump and a quadrupole mass analyzer, capable of measuring speeds up to 100 full scans per second at 20,000 amu/s, without losing sensitivity. The sensitivity is specified with an S/N ratio of >200 for 1 pg OFN, a value that can often be exceeded in practical applications.

In practice, the device is ideal for analyzing volatile molecules, such as short-chain fatty acids or essential oils.

The IR Spirit IR Spectrometer is a Fourier Transform (FT)-IR spectrometer equipped with a QATR unit. The QATR unit allows for the analysis of both liquid and solid substances without the need to press them into a pellet beforehand. Additionally, spectra can be recorded down to a measurement wavenumber of 400 cm-1.

In practice, the device is well-suited for the qualitative analysis of pharmaceuticals (purity control and identity verification) as well as for analyzing biological macromolecules and complex biological components, such as extracellular vesicles.

The Magritek Spinsolve 60 MHz NMR Spectrometer is a benchtop NMR system that operates using a permanent magnet instead of an electromagnet. This system does not rely on liquid helium and is maintenance-free. While the lower magnetic field strength results in reduced resolution and sensitivity compared to high-field instruments, the device is still capable of performing complex 2D measurements using modern pulse programs.

In practice, this spectrometer can be used for tasks such as the structural elucidation of simple molecules, reaction monitoring, and quantification of substances in mixtures.

Our Agilent 7890A GC System is equipped with a 7683B injector system with autosampler and a flame ionization detector (FID), which allows for the detection of any carbon-containing analytes with sufficient volatility. This system is particularly useful for detecting and quantifying alcohols with varying chain lengths.

High-sensitivity HR QTOF MS/MS mass spectrometer with Zeno trap functionality (increasing duty cycle to >90%) and adjustable additional fragmentation capability (electron activated dissociation (EAD) alongside CID). The system also offers true data-independent acquisition (DIA) via the Zeno SWATH function, enabling the creation of comprehensive digital archives with all precursor MS spectra and corresponding fragment MS/MS spectra (MS/MS scan rates up to 133 Hz).

The instrument is well-suited for both quantitative and qualitative workflows involving small molecules, lipids, and proteins. Its applications include forensic-toxicological analysis, general unknown screenings, as well as metabolomics, proteomics, and lipidomics research.

Sensitive triple quadrupole system designed for both quantitative and qualitative applications, with optional QTRAP functionality as a linear ion trap. This allows for the extraction of additional data and insights beyond standard MRM analysis, such as MS/MS/MS (MRM3). It is ideal for the quantification of small molecules from various matrices. Key application areas include therapeutic drug monitoring, forensic screening analysis, pharmaceutical compound research, and clinical research (metabolomics).

The Shimadzu Nexera LC40, EkspertMicro LC 200, Agilent 1200, Exion LC, and Nexera XR CL systems are equipped with various detectors, including UV/VIS, fluorescence, and electrochemical detectors.

Fully automatable sample preparation for CE-IVD certified assays in LC-MS/MS workflows. Applications include sample preparation through protein precipitation and liquid-liquid extraction (LLE) for both quantitative and qualitative analyses.