A5065636199- Cholinesterase and Neurodegenerative Diseases
- Pesticide Exposure and Toxicity
- Computational Drug Discovery Methods
- Chemical synthesis and alkaloids
- Insect and Pesticide Research
- Alkaloids: synthesis and pharmacology
- Environmental Toxicology and Ecotoxicology
- Alzheimer's disease research and treatments
- Medicinal Plants and Neuroprotection
- Nicotinic Acetylcholine Receptors Study
- Pesticide and Herbicide Environmental Studies
- Plant-based Medicinal Research
- Phosphodiesterase function and regulation
- Chemical Reaction Mechanisms
- Berberine and alkaloids research
- Tryptophan and brain disorders
- Synthesis and biological activity
- Education, Psychology, and Social Research
- Inorganic and Organometallic Chemistry
- Microbial Inactivation Methods
- Antimicrobial agents and applications
- Phytochemistry and Bioactive Compounds
- Phytochemistry and Bioactivity Studies
- Hormonal Regulation and Hypertension
- Aldose Reductase and Taurine
University of Defence
2018-2025
University Hospital Hradec Králové
2015-2024
University of Defence
2015-2024
Centre of Advanced Studies
2008-2016
Military University
2016
University of Hradec Králové
2016
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2014
University of Pavol Jozef Šafárik
2013
Assay of acetylcholinesterase (AChE) activity plays an important role in diagnostic, detection pesticides and nerve agents, vitro characterization toxins drugs including potential treatments for Alzheimer’s disease. These experiments were done order to determine whether indoxylacetate could be adequate chromogenic reactant AChE assay evaluation. Moreover, the results compared standard Ellman’s method. We calculated Michaelis constant Km (2.06 × 10−4 mol/L acetylthiocholine 3.21 10−3...
Coupling of two distinct pharmacophores, tacrine and trolox, endowed with different biological properties, afforded 21 hybrid compounds as novel multifunctional candidates against Alzheimer's disease. Several them showed improved inhibitory properties toward acetylcholinesterase (AChE) in relation to tacrine. These hybrids also scavenged free radicals. Molecular modeling studies tandem kinetic analysis exhibited that these target both catalytic active site well peripheral anionic AChE. In...
A series of novel tacrine derivatives and tacrine-coumarin heterodimers were designed, synthesized, biologically evaluated for their potential inhibitory effect on both acetylcholinesterase (AChE) butyrylcholinesterase (BuChE). Of these compounds, heterodimer 7c derivative 6b found to be the most potent inhibitors human AChE (hAChE), demonstrating IC50 values 0.0154 0.0263 μM. Ligands 6b, 6c, exhibited highest levels activity against BuChE (hBuChE), that range from 0.228 0.328 Docking...
Abstract A-series agent A-234 belongs to a new generation of nerve agents. The poisoning former Russian spy Sergei Skripal and his daughter in Salisbury, England, March 2018 led the inclusion other agents into Chemical Weapons Convention. Even though five years have already passed, there is still very little information on its chemical properties, biological activities, treatment options with established antidotes. In this article, we first assessed stability neutral pH for subsequent...
Tacrine (THA), a long withdrawn drug, is still popular scaffold used in medicinal chemistry, mainly for its good reactivity and multi-targeted effect. However, THA-associated hepatotoxicity an issue must be considered drug discovery based on the THA scaffold. Following our previously identified hit compound 7-phenoxytacrine (7-PhO-THA), we systematically explored chemical space with 30 novel derivatives, focus low hepatotoxicity, anticholinesterase action, antagonism at GluN1/GluN2B subtype...
Based on in vitro and vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective treatment of tabun poisonings than currently fielded oximes.
The search for novel drugs to address the medical needs of Alzheimer's disease (AD) is an ongoing process relying on discovery disease-modifying agents. Given complexity disease, such aim can be pursued by developing so-called multi-target directed ligands (MTDLs) that will impact pathophysiology more comprehensively. Herewith, we contemplated therapeutic efficacy amiridine drug acting as a cholinesterase inhibitor converting it into class MTDLs. Applying linking approach, have paired core...
Alzheimer’s disease (AD) is a complex neurodegenerative disorder with an unclear etiology. Current treatments, primarily cholinesterase (ChE) inhibitors and N-methyl-D-aspartate receptor (NMDAR) antagonists, offer only symptomatic relief. Drugs targeting one pathological condition have generated limited efficacy. Thus, combining two or more therapeutic interventions into molecule believed to provide higher benefits for the treatment of AD. In this study, we designed, synthesized,...
A novel series of 6-chlorotacrine-scutellarin hybrids was designed, synthesized and the biological activity as potential anti-Alzheimer’s agents assessed. Their inhibitory towards human acetylcholinesterase (hAChE) butyrylcholinesterase (hBChE), antioxidant activity, ability to cross blood-brain barrier (BBB) hepatotoxic profile were evaluated in vitro. Among these compounds, hybrid K1383, bearing two methylene tether between basic scaffolds, found be very potent hAChE inhibitor (IC50 = 1.63...
Alzheimer's disease (AD) is a debilitating progressive neurodegenerative disorder that ultimately leads to the patient's death. Despite fact novel pharmacological approaches endeavoring block process are still emerging, none of them have reached use in clinical practice yet. Thus, palliative treatment represented by acetylcholinesterase inhibitors (AChEIs) and memantine only therapeutics used. Following multi-target directed ligands (MTDLs) strategy, herein we describe synthesis, biological...
Thirteen known (1–12 and 16) three previously undescribed Amaryllidaceae alkaloids of belladine structural type, named carltonine A-C (13–15), were isolated from bulbs Narcissus pseudonarcissus cv. Carlton (Amaryllidaceae) by standard chromatographic methods. Compounds in sufficient amounts, not tested previously, evaluated for their vitro acetylcholinesterase (AChE; E.C. 3.1.1.7), butyrylcholinesterase (BuChE; 3.1.1.8) prolyl oligopeptidase (POP; 3.4.21.26) inhibition activities....
Two new isoquinoline alkaloids, named fumaranine (2) and fumarostrejdine (10), along with 18 known alkaloids were isolated from aerial parts of Fumaria officinalis. The structures the compounds elucidated on basis spectroscopic analyses by comparison literature data. absolute configuration compound 2 was determined comparing its circular dichroism spectra those analogs. Compounds in sufficient amounts evaluated for their acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase...
Abstract Novel indolotacrine analogues were designed, synthesized, and evaluated as potential drugs for the treatment of Alzheimer's disease. By using a multitarget‐directed ligand approach, compounds designed to act simultaneously cholinesterase (ChE) monoamine oxidase (MAO) inhibitors. The also antioxidant, cytotoxic, hepatotoxic, blood–brain barrier (BBB) permeability properties. Indolotacrine 9 b (9‐methoxy‐2,3,4,6‐tetrahydro‐1 H ‐indolo[2,3‐ ]quinolin‐11‐amine) showed most promising...
In recent studies, several alkaloids acting as cholinesterase inhibitors were isolated from Corydalis cava (Papaveraceae). Inhibitory activities of (+)-thalictricavine (1) and (+)-canadine (2) on human acetylcholinesterase (hAChE) butyrylcholinesterase (hBChE) evaluated with the Ellman's spectrophotometric method. Molecular modeling was used to inspect binding mode compounds into active site pocket hAChE. The possible permeability 1 2 through blood⁻brain barrier (BBB) predicted by parallel...
Tacrine (THA), the first clinically effective acetylcholinesterase (AChE) inhibitor and approved drug for treatment of Alzheimer's disease (AD), was withdrawn from market due to its side effects, particularly hepatotoxicity. Nowadays, THA serves as a valuable scaffold design novel agents potentially applicable AD treatment. One such compound, namely 7-methoxytacrine (7-MEOTA), exhibits an intriguing profile, having suppressed hepatotoxicity concomitantly retaining AChE inhibition properties....