A5064116973- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Synthesis and biological activity
- Chemical synthesis and alkaloids
- Cancer therapeutics and mechanisms
- Alzheimer's disease research and treatments
- Bioactive Compounds and Antitumor Agents
- Synthesis and Biological Evaluation
- Pesticide Exposure and Toxicity
- Phenothiazines and Benzothiazines Synthesis and Activities
- Nicotinic Acetylcholine Receptors Study
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Protein Structure and Dynamics
- DNA and Nucleic Acid Chemistry
- Synthesis and bioactivity of alkaloids
- Chemical Reaction Mechanisms
- Enzyme Structure and Function
- Medicinal Plants and Neuroprotection
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Click Chemistry and Applications
- Metal complexes synthesis and properties
- Genomics, phytochemicals, and oxidative stress
- Axial and Atropisomeric Chirality Synthesis
- Electrochemical Analysis and Applications
- Coordination Chemistry and Organometallics
University of Pavol Jozef Šafárik
2011-2024
Institute of Chemistry of the Slovak Academy of Sciences
2011-2021
Institute of Chemistry
2019
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...
Numerous physiological processes happening in the human body, including cerebral development and function, require participation of biometal ions such as iron, copper, zinc. Their dyshomeostasis may, however, contribute to onset Alzheimer's disease (AD) potentially other neurodegenerative diseases. Chelation is therefore a therapeutic strategy against AD. This review provides survey natural synthetic chelating agents that are or could be used target metal hypothesis Since not only...
The review summarizes research into the highly relevant topics of cholinesterase and amyloid aggregation inhibitors connected to tacrine congeners, both which are associated with neurogenerative diseases. Various opinions will be discussed regarding dual binding site characterized by increased inhibitor potency against acetylcholin/butyrylcholine esterase formation. It is suggested that these compounds can raise levels acetylcholine active site, also prevent aggregation. In connection this...
A549 human lung carcinoma cell lines were treated with a series of new drugs both tacrine and coumarin pharmacophores (derivatives 1a–2c) in order to test the compounds’ ability inhibit cancer growth topoisomerase I II activity. The (hTOPI) relax supercoiled plasmid DNA presence various concentrations tacrine-coumarin hybrid molecules was studied agarose gel electrophoresis. biological activities derivatives using MTT assays, clonogenic cycle analysis quantification number viability. content...
Coumarins are naturally occurring phytochemicals with heterocyclic structures which display a wide range of biological activities against neurological diseases such as Alzheimer´s disease (AD). This study reviews recent research into the design, synthesis and pharmacological profile several series synthetic coumarin ligands clearcholinesterase, assesses monoamino oxidases (MAO-A MAO-B) inhibitory activity, Aβ anti-aggregation potency antioxidant properties reported for these novel...
A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12–17 urea heterodimers 18–22, measure interference type I II topoisomerases. Their profile also inspected in vitro on the HL-60 cell line using different flow cytometric (cell cycle distribution, detection mitochondrial membrane potential dissipation, analysis metabolic activity/viability). The compounds exhibited a profound...
Novel tacrine congeners with side ligands suitable for optimal interaction the peripheral and catalytic sites of acetyl-and butyrylcholinesterase (AChE BuChE) have been synthesized using either 9-isothiocyanato-1,2,3,4-tetrahyhroacridine or 9-chloro-1,2,3,4-tetrahydroacridine which represent convenient synthons by reaction various substituted amines.The compounds were tested their inhibition AChE BuChE whereby a morpholine furfuryl derivative found to be most potent inhibitors, respectively,...
The design of new heterodimeric dual binding site acetylcholinesterase inhibitors constitutes the main goal-directed to development anticholinesterase agents with expanded pharmacological profile. Multi-target compounds are usually designed by combining in a hybrid molecule two or more pharmacophoric moieties that known enable interaction selected molecular targets.All were tested for their inhibitory activity on human AChE/BChE. Ellman´s method was used determine inhibition kinetics and...
Acridine derivatives were first used as antibacterial and antiparasitic agents, later antimalarial anti-HIV drugs, now potentially anti-cancer agents due to their high cytotoxic activity. Due serious adverse effects, new synthetic introduced tested based on modified naturally occurring substances, such acridone derivatives, which also exhibit potential anti-tumor Most of them are DNA-damaging causing relatively strong selective destruction tumor cells. We have in vitro anti-proliferative...
The authors report on the synthesis and biological evaluation of new compounds whose structure combines tacrine indole moieties. Tacrine-indole heterodimers were designed to inhibit cholinesterases β-amyloid formation, cross blood-brain barrier. most potent acetylcholinesterase inhibitors 3c 4d (IC50 = 25 39 nM, respectively). Compound displayed considerably higher selectivity for relative human plasma butyrylcholinesterase in comparison compound (selectivity index: IC50...
A series of novel C4-C7-tethered biscoumarin derivatives (12a–e) linked through piperazine moiety was designed, synthesized, and evaluated biological/therapeutic potential. Biscoumarin 12d found to be the most effective inhibitor both acetylcholinesterase (AChE, IC50 = 6.30 µM) butyrylcholinesterase (BChE, 49 µM). Detailed molecular modelling studies compared accommodation ensaculin (well-established coumarin derivative tested in phase I clinical trials) human recombinant AChE (hAChE) active...
The configuration and dynamic behavior of O-allyl-S-methyl-N-(acridin-9-yl)iminothiocarbonate (1) its S-allyl-O-methyl regioisomer (2) were studied using quantum chemical calculations by applying a novel graphical method to scatter maps obtained from MD simulations for evaluation an NOE-weighted internuclear distance (rNOE). Energy indicated that the Z was predominant each compound and, further, this supported both calculated shifts rNOE. Both N-inversion- rotation-type transition-state...
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Abstract Among all the tacrine congeners synthesized, derivative (III) shows best activity and selectivity against hAChE (Id) hBChE.