A5005243079- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Phosphodiesterase function and regulation
- Pharmacological Receptor Mechanisms and Effects
- Neurotransmitter Receptor Influence on Behavior
- Tryptophan and brain disorders
- Synthesis and Biological Evaluation
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemotherapy-induced cardiotoxicity and mitigation
- Synthesis and biological activity
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Bipolar Disorder and Treatment
- Crystallization and Solubility Studies
- Chemical synthesis and alkaloids
- X-ray Diffraction in Crystallography
- Bioactive Compounds and Antitumor Agents
- Stress Responses and Cortisol
- Aldose Reductase and Taurine
- Analytical Chemistry and Chromatography
- Chemical Synthesis and Analysis
- Enzyme function and inhibition
- Pharmacology and Obesity Treatment
- Antiplatelet Therapy and Cardiovascular Diseases
Jagiellonian University
2015-2024
Medicina
2015-2024
Adamed (Poland)
2020
Institute of Medicinal Plant Development
2016
Lukasiewicz Research Network - Krakow Institute of Technology
2011
In order to target behavioral and psychological symptoms of dementia (BPSD), we used molecular modeling-assisted design obtain novel multifunctional arylsulfonamide derivatives that potently antagonize 5-HT(6/7/2A) D2 receptors, without interacting with M1 receptors hERG channels. vitro studies confirmed their antagonism 5-HT(7/2A) weak interactions key antitargets (M1R hERG) associated side effects. Marked 5-HT6 receptor affinities were also observed, notably for...
Recent breakthroughs in crystallographic studies of G protein-coupled receptors (GPCRs), together with continuous progress molecular modeling methods, have opened new perspectives for structure-based drug discovery. A crucial enhancement this area was development induced fit docking procedures that allow optimization binding pocket conformation guided by the features its active ligands. In course our research program aimed at discovery novel antipsychotic agents, attention focused on...
Alzheimer's disease (AD) is a major public health problem, which due to its increasing prevalence and lack of effective therapy or diagnostics. The complexity the AD pathomechanism requires complex treatment, e.g. multifunctional ligands targeting both causes symptoms disease. Here, we present new multitarget-directed combining pharmacophore fragments that provide blockade serotonin 5-HT6 receptors, acetyl/butyrylcholinesterase inhibition, amyloid β antiaggregation activity. Compound 12 has...
5HT6 receptor antagonists offer the potential for safe and effective drugs against obesity, because they can reduce weight without causing serious side effects in cardiovascular system. Also, their anorexic effect is associated with reduced food intake via an enhancement of satiety. In present study we investigated idalopirdine (LuAE58054) a model obesity induced by high-fat diet. To induce rats, animals were treated feed fat content 40 %. Body was controlled amount water consumed...
Obesity, from early childhood onwards, is a common societal problem. The overconsumption of sweet, salty and high-fat products are the main factors that cause excessive weight gain. It therefore necessary to search for new drugs affect satiety centers reduce sense hunger caloric intake. has been suggested blockade 5-HT6 receptors may food intake, since idalopirdine clinically tested, selective 5HT6 receptor antagonist, it was chosen be examined in animal models obesity. activity measured rat...
The lack of an effective treatment makes Alzheimer's disease a serious healthcare problem and challenge for medicinal chemists. Herein we report interdisciplinary research on novel multifunctional ligands targeting proteins processes involved in the development disease: BuChE, 5-HT6 receptors β-amyloid aggregation. Structure-activity relationship analyses supported by crystallography docking studies led to identification fused-type ligand 50, with remarkable balanced potencies against BuChE...
The most troublesome aspects of behavioral and psychological symptoms dementia (BPSD) are nowadays addressed by antidepressant, anxiolytic, antipsychotic drugs, often administered off-label. Considering their modest effectiveness in patients, the increased risk adverse events cognitive decline, there is an unmet need for well-tolerated effective therapy BPSD. We designed synthesized multifunctional ligands characterized vitro as high-affinity partial agonists D2R, antagonists 5-HT6R,...
Novel 1-(1-benzoylpiperidin-4-yl)methanamine derivatives were designed as "biased agonists" of serotonin 5-HT1A receptors. The compounds tested in signal transduction assays (ERK1/2 phosphorylation, cAMP inhibition, Ca2+ mobilization, and β-arrestin recruitment) which identified ERK1/2 phosphorylation-preferring aryloxyethyl derivatives. novel series showed high receptor affinity, >1000-fold selectivity versus noradrenergic α1, dopamine D2, 5-HT2A, histamine H1, muscarinic M1 receptors,...
Multifunctional ligands as an essential variant of polypharmacology are promising candidates for the treatment multi-factorial diseases like Alzheimer's disease. Based on clinical evidence and following paradigm multifunctional we have rationally designed synthesized a series compounds targeting processes involved in development The biological evaluation led to discovery two with favorable pharmacological characteristics ADMET profile. Compounds 17 35 5-HT6R antagonists (Ki = 13 nM Ki 15...
Butyrylcholinesterase (BuChE) and amyloid β (Aβ) aggregation remain important biological target mechanism in the search for effective treatment of Alzheimer's disease. Simultaneous inhibition thereof by application multifunctional agents may lead to improvement terms symptoms causes Here, we present rational design, synthesis, evaluation molecular modelling studies novel series fluorene-based BuChE Aβ inhibitors with drug-like characteristics advantageous Central Nervous System...