A5034604911- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Psychedelics and Drug Studies
- Tryptophan and brain disorders
- Chemical Synthesis and Analysis
- Synthesis and Biological Evaluation
- Stress Responses and Cortisol
- Pharmacological Receptor Mechanisms and Effects
- Fluorine in Organic Chemistry
- Phenothiazines and Benzothiazines Synthesis and Activities
- Click Chemistry and Applications
- Memory and Neural Mechanisms
- Mental Health Research Topics
- Treatment of Major Depression
- Computational Drug Discovery Methods
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Nicotinic Acetylcholine Receptors Study
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Sulfur-Based Synthesis Techniques
- Attention Deficit Hyperactivity Disorder
- Quinazolinone synthesis and applications
Maj Institute of Pharmacology
2016-2024
Polish Academy of Sciences
2016-2024
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2022
Medicina
2019
Faculty (United Kingdom)
2018
Jagiellonian University
2018
Institute of Pharmacology
2016-2018
Major depressive disorder is a complex disease resulting from aberrant synaptic plasticity that may be caused by abnormal serotonergic signaling. Using combination of behavioral, biochemical, and imaging methods, we analyze 5-HT7R/MMP-9 signaling dendritic spine in the hippocampus mice treated with selective 5-HT7R agonist (LP-211) model chronic unpredictable stress (CUS)-induced depressive-like behavior. We show acute activation induces behavior an MMP-9-dependent manner post mortem brain...
Ketamine and psilocybin belong to the rapid-acting antidepressants but they also produce psychotomimetic effects including timing distortion. It is currently debatable whether these are essential for their therapeutic actions. As depressed patients report that "time dragging," we hypothesized ketamine psilocybin-like compounds may an opposite effect, i.e., time underestimation, purportedly contributing properties.Timing was tested following administration of (R)- (S)-ketamine, psilocybin,...
Abstract Rationale Our study aimed to unravel the unknown mechanisms behind exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) as normative comparison, we investigated behavioral neuroplasticity-related responses PSI, striving shed light distinctive features its antidepressant effects. Objectives We set out assess impact acute prolonged PSI administration WKY WIS rats, employing...
A virtual screening campaign aimed at finding structurally new compounds active 5-HT6R provided a set of candidates. Among those, one structure, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (1, Ki = 91 nM), was selected as hit for further optimization. As expected, the chemical scaffold compound significantly different from all serotonin receptor ligands published to date. Synthetic efforts, supported by molecular modelling, 43 representing...
Close structural analogues of 5-carboxamidotryptamine (5-CT) based on the newly discovered indole-imidazole scaffold were synthesized and evaluated to search for a 5-HT<sub>7</sub> receptor agonist higher selectivity.
Following the glutamatergic theory of schizophrenia and based on our previous study regarding antipsychotic-like activity mGlu7 NAMs, we synthesized a new compound library containing 103 members, which were examined for NAM in T-REx 293 cell line expressing recombinant human receptor. Out twenty-two scaffolds examined, active compounds found only within quinazolinone chemotype. 2-(2-Chlorophenyl)-6-(2,3-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (A9-7, ALX-171, IC50 = 6.14 µM) was...
A series of 5-aryl-1-alkylimidazole derivatives was synthesized using the van Leusen multicomponent reaction. The chemotype is first example low-basicity scaffolds exhibiting high affinity for 5-HT7 receptor together with agonist function. chosen lead compounds 3-(1-ethyl-1H-imidazol-5-yl)-5-iodo-1H-indole (AGH-107, 1o, K i = 6 nM, EC50 19 176-fold selectivity over 5-HT1AR) and 1e (5-methoxy analogue, 30 60 nM) exhibited related CNS targets, metabolic stability low toxicity in HEK-293 HepG2...
The development of compounds with enhanced activity and selectivity by a conserved spatial orientation the pharmacophore elements has long history in medicinal chemistry. Rigidified are an example this concept. However, intramolecular interactions were seldom used as basis for conformational restraints. Here, we show weak that contribute to relatively well-conserved geometry N1-arylsulfonyl indole derivatives. structure analysis along quantum mechanics calculations revealed crucial impact...
In this letter, we report the synthesis of a pyrano[2,3,4-cd]indole chemical scaffold designed through tandem bioisostere generation/virtual screening protocol in search 5-HT6R ligands. The discovered resulted design highly active basic and nonbasic ligands (5-HT6R Ki = 1 nM for compound 6b 4 its neutral analog 7b). Additionally, molecular modeling suggested that hydroxyl group 7a–7d forms hydrogen bonds with aspartic acid D3×32 or D7.36×35.
A hybrid bioisostere generation/virtual screening method combined with narrowing of chemical space through similarity to compounds that are active at the second target was successfully applied for development dual 5-HT<sub>6</sub>/D<sub>2</sub> receptor ligands.
Like other psychedelics, D-lysergic acid diethylamide (LSD) affects numerous serotonin receptors, and according to the current dogma, 5-HT2A receptors are considered main target for its hallucinogenic effects. LSD, however, also displays agonistic activity at 5-HT5A which mediate some of LSD-induced behavioural effects.Using male Sprague Dawley rats, we examined effects receptor antagonists on stimulus control in two-lever drug discrimination test using a FR10 schedule reinforcement.In...
Abstract There is some evidence that the serotonin receptor subtype 7 (5-HT ) could be new therapeutic target for neuroprotection. The aim of this study was to compare neuroprotective and neurite outgrowth potential 5-HT agonists (AH-494, AGH-238, AGH-194) with 5-CT (5-carboxyamidotryptamine) in human neuroblastoma SH-SY5Y cells. results revealed mRNA expression significantly higher retinoic acid (RA)-differentiated cells when compared undifferentiated ones it cell cultured experimental...
Stress resilience is the ability of neuronal networks to maintain their function despite stress exposure. Using a mouse model we here investigate phenomenon. To assess resilient and anhedonic behavioral phenotypes developed after induction chronic unpredictable stress, quantitatively characterized structural functional plasticity excitatory synapses in hippocampus using combination proteomic, electrophysiological, imaging methods. Our results indicate that an active multifactorial process...
Stress resilience is the ability of neuronal networks to maintain their function despite stress exposure. Using a mouse model we investigate phenomenon. To assess resilient and anhedonic behavioral phenotypes developed after induction chronic unpredictable stress, quantitatively characterized structural functional plasticity excitatory synapses in hippocampus using combination proteomic, electrophysiological, imaging methods. Our results indicate that an active multifactorial process...