A5078320587- Carbohydrate Chemistry and Synthesis
- Crystallization and Solubility Studies
- Click Chemistry and Applications
- DNA and Nucleic Acid Chemistry
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Reactions
- Advanced biosensing and bioanalysis techniques
- Chemical Synthesis and Analysis
- Adenosine and Purinergic Signaling
- Biochemical and Molecular Research
- RNA Interference and Gene Delivery
- Sulfur-Based Synthesis Techniques
- Fluorine in Organic Chemistry
- Synthesis and Characterization of Heterocyclic Compounds
- Protein Structure and Dynamics
- HIV/AIDS drug development and treatment
- Polyamine Metabolism and Applications
- Sulfur Compounds in Biology
- Synthesis and Biological Evaluation
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Nanoparticle-Based Drug Delivery
- Retinal Development and Disorders
University of Debrecen
2016-2025
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an enormous challenge to health care systems and medicine. As a result of global research efforts aimed at preventing effectively treating SARS-CoV-2 infection, vaccines with fundamentally new mechanisms action some small-molecule antiviral drugs targeting key proteins in the viral cycle have been developed. most effective drug approved date for treatment is PaxlovidTM, which...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, highly conserved and plays a critical role in ability virus to evade immune system. NendoU promising target for development new antiviral drugs. However, complexity enzyme's structure kinetics, along with broad range recognition sequences lack structural complexes, hampers inhibitors. Here, we performed enzymatic...
Abstract Hydrogen sulfide (H 2 S) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-H S-donor hybrid molecules were prepared by conjugating nucleoside biomolecules a thiol-activatable dithioacetyl group. 5′-Dithioacetate derivatives synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine thymidine), putative 5′-thio metabolites also produced uridine adenosine. According to our measurements...
Abstract α‐Glycosyl thiols are key building blocks for the formation of stable thioglycoside mimetics widespread and biologically relevant α‐ O ‐glycosides, which urges their efficient synthesis. Here, we demonstrate that photoinitiated radical‐mediated addition thioacetic acid to 2‐substituted glycals followed by selective S ‐deacetylation is a generally applicable fully stereoselective method synthesis 1,2‐ cis ‐α‐glycosyl thiols. The low reactivity in radical reaction was overcome...
Sugar-modified nucleosides are prime synthetic targets in anticancer and antiviral drug development. Radical mediated thiol-ene coupling was applied for the first time on nucleoside enofuranoside derivatives to produce a broad range of thio-substituted d-ribo, -arabino, -xylo l-lyxo configured pyrimidine nucleosides. In contrast analogous reactions simple sugar exomethylenes, surprisingly, hydrothiolation alkenes under standard conditions various initiation methods showed low moderate yields...
Abstract The photoinitiated thiol‐ene coupling reactions of 2‐substituted glycals were studied as a generally applicable strategy for stereoselective 1,2‐ cis ‐α‐thioconjugation. Although all reacted with full α‐selectivity, the efficacy varied in broad range depending on their configuration and bearing axial acetoxy substituents very low at room temperature. study revealed that reaction progress could be promoted by cooling inhibited heating. At −80 °C, equilibrium rapidly reversible...
A synergistic effect of BF<sub>3</sub>·Et<sub>2</sub>O, hexafluoroisopropanol and triethylsilane led to efficient detritylation nucleoside, monosaccharide amino acid derivatives.
A comprehensive optimization and mechanistic study on the photoinduced hydrothiolation of different d- l- hexo- pentoglycals with various thiols was performed, at temperature range RT to -120 °C. Addition onto 2-substituted hexoglycals proceeded complete 1,2-cis-α-stereoselectivity in all cases. Hydrothiolation resulted mixtures 1,2-cis-α- -β-thioglycosides varying ratio depending configuration reactants. unsubstituted glycals -80 °C excellent yields and, except for galactal, provided...
The synthesis of oligonucleotide analogues consisting morpholino and a ribo- or deoxyribonucleoside in which the 5'-amino group nucleoside unit provides nitrogen to morpholine ring is described.
Abstract Drug-resistant Plasmodium falciparum ( Pf ) infections are a major burden on the population and healthcare system. The establishment of resistance to most existing antimalarial therapies has complicated problem, emergence artemisinin derivatives is even more concerning. It increasingly difficult cure malaria patients due limited availability effective drugs, resulting in an urgent need for efficacious affordable treatments eradicate this disease. Herein, new nucleoside analogues...
The first concise and efficient synthesis of some fluorine-containing morpholino nucleosides has been developed. One synthetic strategy was based on the oxidative ring cleavage vicinal diol unit uridine, cytidine adenosine guanosine derivatives, followed by cyclisation dialdehyde intermediates double reductive amination with fluorinated primary amines to obtain various N-fluoroalkylated morpholinos. Another approach involved diformyl ammonia source, dithiocarbamate formation...
Cysteinyl nucleoside and homonucleoside oligomers, the first representatives of a new class artificial nucleic acid family were prepared.
A small library of 3'-deoxy-C3'-substituted xylofuranosyl-pyrimidine nucleoside analogues were prepared by photoinduced thiol-ene addition various thiols, including normal and branched alkyl-, 2-hydroxyethyl, benzyl-, sugar to 3'-exomethylene derivatives 2',5'-di-O-tert-butyldimethylsilyl-protected ribothymidine uridine. The bioactivity these was studied on tumorous SCC (mouse squamous carcinoma cell) immortalized control HaCaT (human keratinocyte) cell lines. Several alkyl-substituted...
Radical-mediated hydrothiolation of enoses was studied as a stereoselective method for synthesizing challenging oligosaccharide structures. Three types glycals were reacted with various thiols using UV irradiation at the temperature range rt to −120 °C, producing 39 thioglycosides up tetrasaccharide. Cooling always proved be beneficial efficacy, −80 °C being optimal in most cases. The different conformational preferences intermediate carbon-centered radicals crucial stereoselectivity...
Pleuromutilin is a fungal diterpene natural product with antimicrobial properties, semisynthetic derivatives of which are used in veterinary and human medicine. The development bacterial resistance to pleuromutilins known be very slow, makes the tricyclic skeleton pleuromutilin attractive starting structure for new antibiotic that unlikely induce resistance. Here, we report first synthetic modifications lefamulin at alkene position C19-C20, by two different photoinduced addition reactions,...
d-Arabinofuranosyl-pyrimidine and -purine nucleoside analogues containing alkylthio-, acetylthio- or 1-thiosugar substituents at the C2' position were prepared from corresponding 3',5'-O-silylene acetal-protected 2'-exomethylenes by photoinitiated, radical-mediated hydrothiolation reactions. Although stereochemical outcome of depended on structure both thiol furanoside aglycone, in general, high d-arabino selectivity was obtained. The cytotoxic effect arabinonucleosides studied tumorous SCC...
Abstract SARS-CoV-2 is the causative agent of COVID-19. The highly conserved viral NSP15 endoribonuclease, NendoU, a key enzyme involved in immune evasion, and promising target for development new classes antivirals. Yet, broad variety recognition sequences, complex assembly kinetics, lack structural complexes hampers competitive or allosteric inhibitors this target. Here, we performed enzymatic characterization NendoU its monomeric hexameric form, showing that hexamers are enzymes with...
Background/Aim: Conventional viability tests, help to screen the cellular effects of candidate molecules, but endpoint these measurements lacks sufficient information regarding molecular aspects. A non-invasive, easy-to-setup live-cell microscopic method served in-depth analysis mechanisms potential anticancer drugs. Materials and Methods: The proposed combining MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test with time-lapse scanning microscopy (TLS), provided...
<title>Abstract</title> Hydrogen sulfide (H<sub>2</sub>S) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-H<sub>2</sub>S-donor hybrid molecules were prepared by conjugating nucleoside biomolecules a thiol-activatable dithioacetyl group. 5'-Dithioacetate derivatives synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine thymidine), putative 5'-thio metabolites also produced uridine...
Hypoxanthine-tricyclano is a synthetic adenosine analogue, in which adenine and ribose have been replaced by hypoxanthine morpholino-derived tricyclic moiety, respectively. We investigated whether hypoxanthine-tricyclano could influence atrial inotropy and/or chronotropy, two important functions regulated the A1 receptor, main receptor type of supraventricular myocardium. Paced left atria spontaneously beating right atria, isolated from male, 30-35 weeks old, Wistar rats, were used. The ino-...
Abstract Leloir glycosyltransferases play an important role in many fundamental processes of living systems by catalyzing biological glycosylations. Neutral analogues nucleotide sugars, as potential donor‐substrate inhibitors glycosyltransferases, are prime interest medicinal chemistry. We report the development S ‐linked sugar‐nucleotide replacing α‐ O ‐pyrophosphate bridge with electroneutral ethyl or propyl linker radical mediated hydrothiolation 2‐substituted glycals and olefinic...