A5008486745- Phenothiazines and Benzothiazines Synthesis and Activities
- Receptor Mechanisms and Signaling
- Mast cells and histamine
- Synthesis and Biological Evaluation
- Chemical Synthesis and Analysis
- Neuroscience and Neuropharmacology Research
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Reactions of Organic Compounds
- Cholinesterase and Neurodegenerative Diseases
- X-ray Diffraction in Crystallography
- Click Chemistry and Applications
- Crystallization and Solubility Studies
- Pharmacological Receptor Mechanisms and Effects
- Neurotransmitter Receptor Influence on Behavior
- Phosphodiesterase function and regulation
- Chemical synthesis and alkaloids
- Chemical Reaction Mechanisms
- Epilepsy research and treatment
- Ion channel regulation and function
- Pain Management and Placebo Effect
- Plant chemical constituents analysis
- Synthesis and Biological Activity
- Synthesis of heterocyclic compounds
- Pharmacological Effects and Toxicity Studies
- Neurology and Historical Studies
Jagiellonian University
2016-2023
Cracow University of Technology
2018
Among serotonin receptors, the 5-HT6 subtype is most controversial and least known in field of molecular mechanisms. The 5-HT6R ligands can be pivotal for innovative treatment cognitive impairment, but none has reached pharmacological market, predominantly, due to insufficient “druglikeness” properties. Recently, 1,3,5-triazine-piperazine derivatives were identified as a new chemical family potent ligands. For active triazine agents found (1–4), wider binding profile comprehensive vitro...
Since the year 1993, when 5-HT7 receptor (5-HT7 R) was discovered, there is no selective R ligand introduced to pharmaceutical market. One out of main reasons disqualifying ligands weak drugability properties, including metabolic instability or low permeability. This study focused on search a lead compound by "drug-likeness" estimation first series and potent among 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-aryl-piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione derivatives (11-16). The most...
Antimicrobial resistance (AMR) represents a hot topic in drug discovery. Besides the identification of new antibiotics, use nonantibiotic molecules to block mechanisms is powerful alternative. Bacterial efflux pumps exert an early step AMR development by allowing bacteria grow at subinhibitorial concentrations. Thus, pump inhibitors (EPIs) offer great opportunity fight AMR. Given our experience developing Staphylococcus aureus NorA EPIs, this work, starting from 2-phenylquinoline hit 1, we...
Recently, compound KA-11 was identified as a promising candidate for new broad-spectrum anticonvulsant. This revealed wide protective activity across the most important animal models of seizures such maximal electroshock test (MES), subcutaneous pentylenetetrazole (scPTZ), and six-hertz (6 Hz, 32 mA). Importantly, devoid acute neurological activity, which assessed by applying chimney (TD50 value higher than 1500 mg/kg). The preliminary in vivo results confirmed favorable anticonvulsant...
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.
We developed a focused set of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant and antinociceptive properties. These compounds demonstrated broad-spectrum protective activity in range mouse models, such as the maximal electroshock (MES) test, pentylenetetrazole-induced seizures (scPTZ), 6 Hz (32 mA) seizures. Compound 22 showed most (ED50 MES = 23.7 mg/kg, ED50 22.4 ED50scPTZ 59.4 mg/kg). In addition, revealed efficacy formalin-induced tonic pain. vivo activities...
A newly developed series of non-imidazole histamine H3 receptor (H3R) antagonists (1–16) was evaluated in vivo for anticonvulsant effects three different seizure models Wistar rats. Among the novel H3R examined, antagonist 4 shortened duration tonic hind limb extension (THLE) a dose-dependent fashion maximal electroshock (MES)-induced and offered full protection against pentylenetetrazole (PTZ)-induced generalized tonic-clonic (GTCS), following acute systemic administration (2.5, 5, 10, 15...
In our recent studies, we identified compound N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) as a broad-spectrum hybrid anticonvulsant which showed potent protection across the most important animal acute seizure models such maximal electroshock (MES) test, subcutaneous pentylenetetrazole (s.c. PTZ) and 6-Hz (32 mA) test in mice. Therefore, AS-1 may be recognized candidate for new effective different types of human epilepsy with favorable safety margin profile determined rotarod aim...
Though the 5-HT6 serotonin receptor is an important target giving both agonists and antagonists similar therapeutic potency in treatment of topic CNS-diseases, no 5-HT6R ligand has reached pharmaceutical market yet due to too narrow chemical space known agents insufficient “drugability.” Recently, a new group non-indole non-sulfone hydantoin-triazine ligands was found, where 3-((4-amino-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-yl)methyl)-5-methyl-5-(naphthalen-2-yl)imidazolidine-2,4-dione...
This study focuses on the design, synthesis, biological evaluation, and computer-aided structure-activity relationship (SAR) analysis for a novel group of aromatic triazine-methylpiperazines, with an hydantoin spacer between 1,3,5-traizine fragment. New compounds were synthesized their affinities serotonin 5-HT₆, 5-HT1A, 5-HT2A, 5-HT₇, dopamine D₂ receptors evaluated. The induced-fit docking (IFD) procedure was performed to explore 5-HT₆ receptor conformation space employing two lead...
Alzheimer's disease (AD) is a complex and incurable illness that requires the urgent approval of new effective drugs. However, since 2003, no molecules have shown successful results in clinical trials, thereby making common "one compound – one target" paradigm questionable. Recently, multitarget-directed ligand (MTDL) approach has gained popularity, as compounds targeting at least two biological targets may be potentially more treating AD. On basis these findings, we designed, synthesized,...
Influence of aromatic rings topology on 5-HT<sub>7</sub>/5-HT<sub>1A</sub>activity, for novel hydantoin derivatives, was examined.
Background: There is currently no drug that slows the process of neurodegeneration or alleviates cognitive and depressive symptoms in patients with Alzheimer’s disease. Due to increasing number patients, there an urgent need develop novel drugs neuroprotective, procognitive, antidepressant properties. Objective: The aim this study was design, synthesize, evaluate aminoalkanamides serotonin 5-HT 1A /5-HT 7 receptor affinity phosphodiesterase (PDE) inhibitory activity as a new approach combat...
In the continuation of our study substituted isocoumarins a series novel 3-azolyl isocoumarin and their thio derivatives, including some related lactone compounds was prepared biologically profiled against C. albicans showing moderate activity with MIC values in range 4?60 ?g mL-1, general. The additional characterisation selected carried out by exploring on CYP3A4 CYP2D6 enzymes, while experiments mutagenicity were performed AMES test. representative 3b, 4a 4b showed lower inhibitory CYP...