A5047714749- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Phenothiazines and Benzothiazines Synthesis and Activities
- Quinazolinone synthesis and applications
- Tuberculosis Research and Epidemiology
- Synthesis and Biological Evaluation
- Synthesis and biological activity
- Cancer therapeutics and mechanisms
- Chemical Synthesis and Analysis
- Mycobacterium research and diagnosis
- Crystallography and molecular interactions
- Chemical synthesis and alkaloids
- Synthesis of β-Lactam Compounds
- Lanthanide and Transition Metal Complexes
- Electron Spin Resonance Studies
- ATP Synthase and ATPases Research
- Analytical Chemistry and Chromatography
- Synthesis and Reactions of Organic Compounds
- Berberine and alkaloids research
- Synthesis and Reactivity of Heterocycles
- Organic Chemistry Cycloaddition Reactions
- Click Chemistry and Applications
- Pharmacogenetics and Drug Metabolism
- Synthetic Organic Chemistry Methods
- Biochemical and Molecular Research
Martin Luther University Halle-Wittenberg
2015-2025
Francke Foundations
2017
University of Eastern Finland
2015
Philipps University of Marburg
1995-2006
Heinrich Heine University Düsseldorf
2006
Robugen (Germany)
2005
Chamazulene carboxylic acid (1) is a natural profen with anti-inflammatory activity and degradation product of proazulenic sesquiterpene lactones, e.g., matricin. Both 1 proazulenes occur in chamomile (Matricaria recutita), yarrow (Achillea millefolium), few other Asteraceae species. It was isolated improved yields, characterized physicochemically, found to be an inhibitor cyclooxygenase-2, but not cyclooxygenase-1. had several animal models local systemic application. When human volunteers...
Abstract Nitro-substituted 1,3-benzothiazinones (nitro-BTZs) are mechanism-based covalent inhibitors of Mycobacterium tuberculosis decaprenylphosphoryl-β-D-ribose-2′-oxidase (DprE1) with strong antimycobacterial properties. We prepared a number oxidized and reduced forms nitro-BTZs to probe the mechanism inactivation enzyme identify opportunities for further chemistry. The kinetics DprE1 was examined using an enzymatic assay that monitored reaction progress up 100 min, permitting compound...
The imidazopyridine telacebec, also known as Q203, is one of only a few new classes compounds in more than 50 years with demonstrated antituberculosis activity humans. Telacebec inhibits the mycobacterial respiratory supercomplex composed complexes III and IV (CIII 2 CIV ). In electron transport chains, CIII replaces canonical CIV, transferring electrons from intermediate carrier menaquinol to final acceptor, molecular oxygen, while simultaneously protons across inner membrane power ATP...
The metabolism of arachidonic acid can be catalyzed by either one two enzyme families; the cyclooxygenases or lipoxygenases. family lipoxygenases is divided into four subtypes according to tissue distribution; 5-, 8-, 12-, and 15-lipoxygenase. 12-lipoxygenase metabolites, such as 12(S)-hydroxyeicosatetraenoic acid, have been found play a central role in various stages metastatic process tumors are, therefore, potential targets for anticancer treatment. A variety lipoxygenase inhibitors...
Abstract Ferroptosis is a form of cell death that has received considerable attention not only as means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation exploited by tumours counteract phospholipid oxidation. Here, we identify pro-ferroptotic activity 7-dehydrocholesterol reductase (DHCR7) and an unexpected pro-survival function its substrate, (7-DHC). Although previous studies suggested high levels 7-DHC are cytotoxic...
Wollamide B is a cationic antimycobacterial cyclohexapeptide that exhibits activity against Mycobacterium bovis (M. bovis) (IC50 of 3.1 μM). Aiming to define its structural relationship (SAR), optimizing potency and pharmacokinetic properties, libraries analogues were synthesized following standard Fmoc-based solid phase peptide synthesis approach. The activities wollamide all the tested tuberculosis (Mtb) H37Rv. Parallely, in vitro drug metabolism (ADME) profiling was done for compounds...
New, more-effective drugs for the treatment of lung disease caused by nontuberculous mycobacteria (NTM) are needed. Among NTM opportunistic pathogens, Mycobacterium abscessus is most difficult to cure and intrinsically multidrug resistant. In a whole-cell screen compound collection active against tuberculosis , we previously identified piperidine-4-carboxamide (P4C) MMV688844 (844) as hit M. .
Ethambutol (EMB) is a first-line anti-tuberculosis drug that also considered in treatment regimens for infections caused by non-tuberculous mycobacteria (NTM). EMB targets the arabinosyl transferases EmbCAB, which are important synthesis of cell wall constituents. To further explore and narrow down structural variability EMB, we synthesized three series new analogs. We tested their activity against Mycobacterium tuberculosis, smegmatis, abscessus intracellulare. Only analogs very closely...
Background/Objectives: Non-replicating persisters (NRPs) of Mycobacterium abscessus are a bacterial subpopulation that can survive in the host under unfavorable conditions, such as hypoxia or nutrient starvation. The eradication these bacteria is difficult, which one reason for long treatment duration and failure. drug discovery process should therefore contain methods to screen activity against NRPs. Methods: A hypoxic environment used generate NRPs M. termed low-oxygen (LOPs). For this, an...
Mycobacterium abscessus is a rapidly growing nontuberculous causing severe pulmonary infections, especially in immunocompromised individuals and patients with underlying lung conditions like cystic fibrosis (CF). While rifamycins are the pillar of tuberculosis treatment, their efficacy against M. disease severely compromised by intrabacterial ADP-ribosylation. Additionally, induce cytochrome P450 3A4 (CYP3A4), major human drug-metabolizing enzyme, further limiting use comorbidities that...
Tissue oxygenation plays an important role in the pathophysiology of various diseases and is often a marker prognosis therapeutic response. EPR (ESR) suitable noninvasive oximetry technique. However, to reliably deploy soluble probes as oxygen sensors complex biological systems, there still need investigate improve their specificity, sensitivity, stability. We reproducibly synthesized derivatives tetrathiatriarylmethyl tetrachlorotriarylmethyl (trityl) radicals. Hydrophilic radicals were...