A5013125520- Cholinesterase and Neurodegenerative Diseases
- Surface Chemistry and Catalysis
- Alcoholism and Thiamine Deficiency
- Molecular Junctions and Nanostructures
- Liver Disease Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Biochemical and Molecular Research
- Biochemical Acid Research Studies
- Synthesis of Organic Compounds
- Synthesis and biological activity
- Surface and Thin Film Phenomena
- Neuroscience and Neuropharmacology Research
- Graphene research and applications
- Computational Drug Discovery Methods
- Natural Antidiabetic Agents Studies
- Alzheimer's disease research and treatments
- Synthesis and Biological Evaluation
- Amino Acid Enzymes and Metabolism
- Click Chemistry and Applications
- Bioactive Compounds and Antitumor Agents
- Epigenetics and DNA Methylation
- Pomegranate: compositions and health benefits
- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- Nicotinic Acetylcholine Receptors Study
University of Gothenburg
2019-2024
Saarland University
2023-2024
KTH Royal Institute of Technology
2023-2024
Science for Life Laboratory
2023-2024
University of Groningen
2015-2023
Instituto de Química Médica
2011-2017
Consejo Superior de Investigaciones Científicas
2012-2017
Bentham Science Publishers (United Arab Emirates)
2013
Bentham Science Publishers (China)
2013
By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer's disease (AD), a new family tacrine-4-oxo-4H-chromene hybrids has been designed, synthesized, evaluated biologically. The tacrine fragment was selected its inhibition cholinesterases, flavonoid scaffold derived from 4-oxo-4H -chromene chosen radical capture β-secretase 1 (BACE-1) inhibitory activities. At nano- picomolar concentrations, inhibit human acetyl- butyrylcholinesterase (h-AChE...
We report the synthesis, theoretical calculations, antioxidant, anti-inflammatory, and neuroprotective properties, ability to cross blood-brain barrier (BBB) of (Z)-α-aryl heteroaryl-N-alkyl nitrones as potential agents for stroke treatment. The majority compete with DMSO hydroxyl radicals, most them are potent lipoxygenase inhibitors. Cell viability-related (MTT assay) studies clearly showed that 1-3 10 give rise significant neuroprotection. When compounds 1-11 were tested necrotic cell...
Abstract The energy-coupling factor (ECF) transporters are a family of transmembrane proteins involved in the uptake vitamins wide range bacteria. Inhibition activity these could reduce viability pathogens that depend on vitamin uptake. central role transport metabolism bacteria and absence from humans make ECF an attractive target for inhibition with selective chemical probes. Here, we report identification promising class inhibitors transporters. We used coarse-grained molecular dynamics...
Amyloid beta (Aβ) aggregation and deposition is a key pathological hallmark of AD. Growing evidence suggests that neurotoxicity this peptide related to the formation toxic oligomeric aggregates. Therefore, deeply investigated therapeutic strategy comes at present from blocking these species non-toxic Among other considered strategies, multi-target approach has been proposed as more suitable potential therapy, precisely due multifactorial nature In context, we recently identified ASS234,...
We report the formation of one- and two-dimensional metal–organic coordination structures from para-hexaphenyl-dicarbonitrile (NC–Ph6–CN) molecules Cu atoms on graphene epitaxially grown Ir(111). By varying stoichiometry between NC–Ph6–CN atoms, dimensionality could be tuned: for a 3:2 ratio, hexagonal porous network based threefold was observed, while 1:1 one-dimensional chains twofold were formed. The metal–ligand bonds supported by imaging within with scanning tunneling microscopy....
We present the a homology model of<italic>M. tuberculosis</italic>DXS that we validated by identifying thiamine and diphosphate analogues as potent inhibitors of DXS.
The ESKAPE bacteria are the six highly virulent and antibiotic-resistant pathogens that require most urgent attention for development of novel antibiotics. Detailed knowledge target proteins specific to is essential develop treatment options. methylerythritol-phosphate (MEP) pathway, which absent in humans, represents a potentially valuable Within MEP enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXPS) catalyzes crucial, rate-limiting first step branch point biosynthesis vitamins B1 B6. We...
Benzothiazepine CGP37157 is widely used as tool to explore the role of mitochondria in cell Ca(2+) handling, by its blocking effect Na(+)/Ca(2+) exchanger. Recently, has shown exhibit neuroprotective properties. In trend improve neuroprotection profile, we have synthesized ITH12505, an isosteric analogue having a methyl instead chlorine at C2' phenyl ring. ITH12505 exerted properties similar chromaffin cells and hippocampal slices stressed with veratridine. Also, both compounds afforded...
Abstract Energy‐coupling factor (ECF) transporters are membrane‐protein complexes that mediate vitamin uptake in prokaryotes. They bind the substrate through action of a specific integral membrane subunit (S‐component) and power transport by hydrolysis ATP three‐subunit ECF module. Here, we have studied binding thiamine derivatives to ThiT, thiamine‐specific S‐component. We designed synthesized ThiT with high affinity; this allowed us evaluate contribution functional groups affinity....
The inhibition of liver pyruvate kinase could be beneficial to halt or reverse non-alcoholic fatty disease (NAFLD), a progressive accumulation fat in the that can lead eventually cirrhosis. Recently, urolithin C has been reported as new scaffold for development allosteric inhibitors (PKL). In this work, comprehensive structure–activity analysis was carried out. More than 50 analogues were synthesized and tested regarding chemical features responsible desired activity. These data pave way...
Exploring binding opportunities in the pocket of ThiT, a S-component for transport thiamine.
Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP production during liver cell glycolysis considered potential drug target for the treatment non-alcoholic fatty disease (NAFLD). In this study, we report first ADP-competitive PKL inhibitors identify several starting points further optimization these inhibitors. Modeling structural biology guided PKL-specific anthraquinone-based compound. A structure–activity relationship study 47 novel synthetic derivatives revealed...
The surface electronic structure is engineered by means of metal–organic networks. We show that on top electron confinement phenomena, the energy state can be controlled <italic>via</italic> adatom coordination density.
Abstract We applied dynamic combinatorial chemistry (DCC) to identify ligands of ThiT, the S‐component energy‐coupling factor (ECF) transporter for thiamine in Lactococcus lactis . used a pre‐equilibrated library (DCL) and saturation‐transfer difference (STD) NMR spectroscopy ThiT. This is first report which DCC fragment growing an ill‐defined pocket, one reports its application with integral membrane protein as target.
Scanning probe microscopy has become an essential tool to not only study pristine surfaces but also on-surface reactions and molecular self-assembly. Nonetheless, due inherent limitations, some atoms or (parts of) molecules are either imaged cannot be unambiguously identified. Herein, we discuss the arrangement of two different nonplanar assemblies para-hexaphenyl-dicarbonitrile (Ph6(CN)2) on Au(111) based a combined theoretical experimental approach. For deposition Ph6(CN)2 kept at room...
This work presents new small molecules that bind to the protein ThiT, which confers substrate specificity Energy-Coupling Factor (ECF) transporter for thiamine. Further development of may lead compounds with antimicrobial activity.
Abstract Chromobox homolog 7 (Cbx7) is an epigenetic modulator that important driver of multiple cancers. It a methyl reader protein operates by recognizing and binding to methylated lysine residues on specific partners. Herein we report our efforts create low‐molecular‐weight inhibitors Cbx7 making rational structural adaptations different protein, L3MBTL1, had previously been reported be inactive against Cbx7. We evaluated each new inhibitor for inhibition fluorescence polarization assay,...
A comparative study on the self-assembly of sexiphenyl-dicarbonitrile highly oriented pyrolytic graphite and single-layer graphene Cu(111) is presented. Despite an overall low molecule-substrate interaction, close-packed structures exhibit a peculiar shift repeating every four to five molecules. This has hitherto not been reported for similar systems hence unique feature induced by graphitic substrates.
Non-alcoholic fatty liver disease (NAFLD) is a prevalent pathological condition characterised by the accumulation of fat in liver. Almost one-third global population affected NAFLD, making it significant health concern. However, despite its prevalence, there currently no approved drug specifically designed for treatment NAFLD. To address this critical gap, researchers have been investigating potential targets NAFLD development. One promising candidate isoform pyruvate kinase (PKL). In recent...