A5026566916- Chemical Synthesis and Analysis
- Synthesis and Biological Evaluation
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and biological activity
- Cancer therapeutics and mechanisms
- Quinazolinone synthesis and applications
- Click Chemistry and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Reactivity of Heterocycles
- Asymmetric Synthesis and Catalysis
- Sulfur-Based Synthesis Techniques
- Synthesis and Catalytic Reactions
- Synthetic Organic Chemistry Methods
- Synthesis of heterocyclic compounds
- Multicomponent Synthesis of Heterocycles
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthesis and pharmacology of benzodiazepine derivatives
- Catalytic C–H Functionalization Methods
- Synthesis and Reactions of Organic Compounds
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Polyamine Metabolism and Applications
- Protein Degradation and Inhibitors
- Analytical Chemistry and Chromatography
Palacký University Olomouc
2016-2025
Institute of Molecular and Translational Medicine
2012-2022
Universidad de Málaga
2018
Leibniz University Hannover
2018
Universidade de Santiago de Compostela
2018
Institute of Organic Chemistry with Centre of Phytochemistry
2018
Bulgarian Academy of Sciences
2018
University of Nottingham
2018
University of Huddersfield
2018
University of Notre Dame
2007-2009
Abstract The human aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that pivotal regulator of physiology and pathophysiology. Allosteric inhibition AhR was previously thought to be untenable. Here, we identify carvones as noncompetitive, insurmountable antagonists characterize the structural functional consequences their binding. Carvones do not displace radiolabeled ligands from binding but instead bind allosterically within bHLH/PAS-A region AhR. influence...
A preloaded resin consisting of a thalidomide moiety and an ethylene-oxy linker allows the simple fast formation PROTACs. The feasibility procedure was illustrated by conjugating different protein kinase inhibitors. biological functionality ibrutinib-like conjugate then confirmed cellular experiment.
Oncogenic mutations in gene encoding FLT3 kinase are often detected acute myeloid leukaemia (AML) patients, and several potent inhibitors have been developed. However, the inhibitor treatment leads to resistance development subsequent relapse. Targeted degradation of oncogenic protein kinases has emerged as a feasible pharmacological strategy, providing more robust effect over traditional competitive inhibitors. Based on previously developed CDK9, we designed prepared novel...
Combinatorial solid-phase synthesis of bis-heterocyclic compounds, characterized by the presence two heterocyclic cores connected a spacer variable length/structure, provided structurally heterogeneous libraries with skeletal diversity. Both rings were assembled on resin in combinatorial fashion.
Abstract A solid‐phase synthetic (SPS) method was developed for the preparation of BODIPY‐labeled bioactive compounds that allows fast and simple synthesis conjugates use in fluorescent microscopy. The approach used to visualize cellular uptake distribution cytotoxic triterpenes cancer cells.
Plant ALDH10 family members are aminoaldehyde dehydrogenases (AMADHs), which oxidize ω-aminoaldehydes to the corresponding acids. They have been linked polyamine catabolism, osmoprotection, secondary metabolism (fragrance), and carnitine biosynthesis. Plants commonly contain two AMADH isoenzymes. We previously studied substrate specificity of isoforms from peas (PsAMADHs). Here, isoenzymes tomato (Solanum lycopersicum), SlAMADHs, three AMADHs maize (Zea mays), ZmAMADHs, were kinetically...
4-Chloro-2-fluoro-5-nitrobenzoic acid is a commercially available multireactive building block that can serve as starting material in heterocyclic oriented synthesis (HOS) leading to various condensed nitrogenous cycles. This work describes its ability for the preparation of substituted heterocycles having 5–7-membered cycles via polymer-supported o-phenylendiamines. Immobilization this compound on Rink resin followed by further chlorine substitution, reduction nitro group and appropriate...
Herein we report the polymer-supported synthesis of 3,4-dihydro-2H-1,4-oxazine-3-carboxylic acid derivatives using immobilized Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH as starting materials. After solid-phase-synthesis N-alkyl-N-sulfonyl/acyl intermediates, target dihydrooxazines were obtained trifluoroacetic acid-mediated cleavage from resin. This approach was also studied for preparation dihydrothiazines Fmoc-Cys(Trt)-OH. Inclusion triethylsilane in cocktail resulted stereoselective formation...
G-protein coupled receptors (GPCRs) exist in an equilibrium of multiple conformational states, including different active which depend on the nature bound ligand. In consequence, states can initiate specific signal transduction pathways. The study identified compound 7e, acts as a potent 5-hydroxytryptamine type 6 receptor (5-HT6R) neutral antagonist at Gs and does not impact neurite growth (process controlled by Cdk5). MD simulations highlighted changes for 7e inverse agonist PZ-1444....
To better understand the mechanism of action antitumor triterpenes, we are developing methods to identify their molecular targets. A promising method is based on combination quantitative proteomics with SILAC and uses active compounds anchored magnetic beads via biotin-streptavidin interaction. We developed a simple fast solid-phase synthetic technique connect terpenes biotin through linker. Betulinic acid was biotinylated from three different conjugation sites for use as standard validation...
C(8)-H direct arylation of purine derivatives immobilized on Wang resin is described. The skeleton was via C(6)-regioselective substitution 2,6-dichloropurine with polymer-supported amines. After N(9)-alkylation two different alkyl iodides and C(2) selected amines, reaction conditions for were developed optimized. Various aryl bromides used the affording target 2,6,8,9-tetrasubstituted purines in very good purity. same also applied synthesis 2,6,8-trisubstituted purines, however, yields...
Solid-phase synthesis of 3,4-dihydro-benzo[e][1,4]diazepin-5-ones with three diversity positions is described. Various primary amines were used as the starting material and immobilized on polystyrene resin equipped different acid-labile linkers. Polymer-supported converted to α-aminoketones use their sulfonylation 4-nitrobenzensulfonylchoride (4-Nos-Cl) subsequent alkylation α-bromoketones. After cleavage 4-Nos group, corresponding acylated various o-nitrobenzoic acids. Reduction nitro group...
Simple solid-phase synthesis of 3,10-dihydro-2H-benzo[e]imidazo[1,2-b][1,2,4]thiadiazin-2-one 5,5-dioxides is described, with Fmoc-α-amino acids and 2-nitrobenzenesulfonyl chlorides (2-NosCls) being the key building blocks. were immobilized on Wang resin transformed to corresponding 2-nitrobenzenesulfonamides in two steps. After reduction nitro group, Fmoc-thioureas synthesized followed by cyclization 1,2,4-benzothiadiazine-1,1-dioxide scaffold diisopropylcarbodiimide (DIC). Cleavage Fmoc...
Abstract Different synthetic approaches leading to compounds containing bicyclic guanidine scaffolds are summarised. Because of the diversity within this group target molecules and wide range individually reported routes, review is divided into three subsections according key intermediate used obtain structure. The first section dedicated strategies in which monocyclic derivatives as intermediates. second presents direct syntheses guanidines from acyclic or non‐guanidine starting materials....
The quality of the most commonly used support for solid-phase syntheses, polystyrene resin cross-linked with 1% divinylbenzene, differs considerably even among different lots from same source. Determination swelling capacity resins before carrying out syntheses represents a very simple means nondestructive presynthetic characterization.
An efficient method is described for the solid-supported synthesis of imidazo[4,5-b]pyridines and imidazo[4,5-c]pyridines from 2,4-dichloro-3-nitropyridine. The key pyridine building block was reacted with polymer-supported amines, followed by replacement second chlorine nitro group reduction, imidazole ring closure aldehydes. Depending on combination solution-phase reagents, strategy allowed simple preparation target trisubstituted derivatives variable positioning nitrogen atom....
Here, we have identified the interaction site of contraceptive drug gamendazole using computational modeling. The was previously described as a ligand for eukaryotic translation elongation factor 1-α 1 (eEF1A1) and found to be potential target derivatives 2-phenyl-3-hydroxy-4(1 H)-quinolinones (3-HQs), which exhibit anticancer activity. this class 3-HQs with eEF1A1 inside cancer cells confirmed via pull-down assay. We designed synthesized new family subsequently applied isothermal titration...