A5017890506- Computational Drug Discovery Methods
- Synthesis and biological activity
- SARS-CoV-2 and COVID-19 Research
- melanin and skin pigmentation
- Receptor Mechanisms and Signaling
- Synthesis of Organic Compounds
- Biochemical Analysis and Sensing Techniques
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Skin Protection and Aging
- Synthesis of Indole Derivatives
- Neuropeptides and Animal Physiology
- Synthesis and Characterization of Heterocyclic Compounds
- Bioactive Compounds and Antitumor Agents
- Chemokine receptors and signaling
- COVID-19 Clinical Research Studies
- Click Chemistry and Applications
- vaccines and immunoinformatics approaches
- Adenosine and Purinergic Signaling
- Synthesis and Biological Evaluation
- Cholesterol and Lipid Metabolism
- Platelet Disorders and Treatments
- Antimicrobial Peptides and Activities
- Multicomponent Synthesis of Heterocycles
- Quinazolinone synthesis and applications
University of Tübingen
2021-2025
University of Bonn
2015-2024
Bernstein Center for Computational Neuroscience Tübingen
2024
Pharmaceutical Biotechnology (Czechia)
2022
Chungnam National University
2009-2020
University of Cambridge
2020
Tokyo University of Pharmacy and Life Sciences
2012-2014
The main protease of SARS-CoV-2 (M
The novel coronavirus, SARS-CoV-2, has been identified as the causative agent for current coronavirus disease (COVID-19) pandemic. 3CL protease (3CLpro) plays a pivotal role in processing of viral polyproteins. We report peptidomimetic compounds with unique benzothiazolyl ketone warhead group, which display potent activity against SARS-CoV-2 3CLpro. most inhibitor YH-53 can strongly block replication. X-ray structural analysis revealed that establishes multiple hydrogen bond interactions...
In recent years, many synthetic cannabinoid (CB) receptor agonists have appeared on the market as constituents of herbal incense mixtures known "spice". Contrary to declared use, they are perorally consumed a replacement for marijuana get "high". cases, detailed information physicochemical and pharmacological properties compounds found in spice preparations is lacking. We now evaluated large series heterocyclic compounds, 1,3-disubstituted indole 2-azaindole derivatives or assumed be CB1...
The Gi protein-coupled receptor GPR84, which is activated by (hydroxy)fatty acids, highly expressed on immune cells. Recently, 3,3'-diindolylmethane was identified as a heterocyclic, nonlipid-like GPR84 agonist. We synthesized broad range of diindolylmethane derivatives condensation indoles with formaldehyde in water under microwave irradiation. products were evaluated at the human cAMP and β-arrestin assays. Structure-activity relationships (SARs) steep. 3,3'-Diindolylmethanes bearing small...
The main protease (Mpro, 3CLpro) of SARS-CoV-2 is an attractive target in coronaviruses because its crucial involvement viral replication and transcription. Here, we report on the design, synthesis, structure-activity relationships novel small-molecule thioesters as Mpro inhibitors. Compounds 3w 3x exhibited excellent inhibition with kinac/Ki 58,700 M-1 s-1 (Ki = 0.0141 μM) 27,200 0.0332 μM), respectively. In Calu-3 Vero76 cells, compounds 3h, 3i, 3l, 3r, 3v, 3w, displayed antiviral activity...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to disease 2019 (COVID-19) pandemic. main protease SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from viral RNA, making it validated target for therapeutics. New chemical phenotypes are frequently discovered in natural goods. In current study, we used fluorogenic assay test variety products their ability inhibit Mpro. Several compounds...
Diindolylmethane (DIM) and its derivatives have recently been in the focus of interest due to their significant biological activities, specifically cancer prevention therapy. Molecular targets DIM identified, e.g., immunostimulatory G protein-coupled receptor GPR84. However, most reported investigated are symmetrical because general methods for obtaining unsymmetrical DIMs lacking. To optimize interaction with protein targets, substitution is required. In present study we developed a new,...
Cathepsins (Cats) are proteases that mediate the successful entry of SARS-CoV-2 into host cells. We designed and synthesized a tailored series 21 peptidomimetics evaluated their inhibitory activity against human cathepsins L, B, S. Structural diversity was realized by combinations different C-terminal warhead functions N-terminal capping groups, while central Leu-Phe fragment maintained. Several compounds were identified as promising cathepsin L S inhibitors with
ACKR3, an atypical chemokine receptor, has been associated with prothrombotic events and the development of cardiovascular events. We designed, synthesized, evaluated a series novel small molecule ACKR3 agonists. Extensive structure–activity relationship studies resulted in several promising agonists potencies ranging from low micromolar to nanomolar range, for example, 23 (EC50 = 111 nM, Emax 95%) 27 69 82%) β-arrestin-recruitment assay. These compounds are selective versus ACKR2, CXCR3,...
The main protease (Mpro) of SARS-CoV-2 is a key drug target for the development antiviral therapeutics. Here, we designed and synthesized series small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent Mpro inhibitors, including 8n (IC50 = 0.0752 μM), 8p 0.0887 8r 0.0199 10a 0.0376 10c 0.0177 10f 0.0130 μM). Most them additionally inhibited cathepsin L also active against SARS-CoV-1 MERS-CoV Mpro. In Calu-3 cells, several 8r,...
Succinate is a pivotal tricarboxylic acid cycle metabolite but also specifically activates the G i ‐ and q ‐coupled succinate receptor 1 (SUCNR1). Contradictory roles of succinate‐SUCNR1 signaling include reports about its anti‐ or pro‐inflammatory effects. The link between cellular metabolism localization‐dependent SUCNR1 qualifies as potential cause for reported conflicts. To systematically address this connection, we used diverse set methods, including several bioluminescence resonance...