Andrzej J. Bojarski
YOU?
Author Swipe
View article: The impact of secondary site interactions on the binding specificity of bitopic dopamine D2/D3 receptor ligands
The impact of secondary site interactions on the binding specificity of bitopic dopamine D2/D3 receptor ligands Open
Dysfunction of dopamine receptors and interruption of normal dopaminergic signaling have been linked to severe neuropsychiatric diseases such as schizophrenia, Parkinson's disease and depression. Although these receptors are among the most…
View article: Novel Dual 5-HT7 Antagonists and Sodium Channel Inhibitors as Potential Therapeutic Agents with Antidepressant and Anxiolytic Activities
Novel Dual 5-HT7 Antagonists and Sodium Channel Inhibitors as Potential Therapeutic Agents with Antidepressant and Anxiolytic Activities Open
Background/Objectives: The study aimed to pharmacologically evaluate dually acting ligands, 5-HT7 antagonists and sodium channel inhibitors, as potential therapeutic agents for the treatment of depression, anxiety, and neuropathic pain. Th…
View article: Intepirdine Derivatives Possessing Dual 5HT6 Antagonism / HDAC6 Inhibitory Activity
Intepirdine Derivatives Possessing Dual 5HT6 Antagonism / HDAC6 Inhibitory Activity Open
Alzheimer's Disease (AD) impacts significantly the quality of life of people aged over 65 years old, while millions more suffer from other types of dementia, yet no effective drugs exist. The few approved drugs in this area address mostly …
View article: Correction: Compound PZ-1262, a 4-isoquinoline-sulfonamide analog of Brexpiprazole, produces potential antidepressant, anxiolytic and procognitive effects in rodent models
Correction: Compound PZ-1262, a 4-isoquinoline-sulfonamide analog of Brexpiprazole, produces potential antidepressant, anxiolytic and procognitive effects in rodent models Open
View article: Identification of Orthosteric GABA<sub>B</sub> Receptor Ligands by Virtual Screening and <i>In Vitro</i> Validation
Identification of Orthosteric GABA<sub>B</sub> Receptor Ligands by Virtual Screening and <i>In Vitro</i> Validation Open
The GABAB receptor (GABAB-R) is a heterodimeric class C G-protein coupled receptor (GPCR) associated with numerous neurological and neuropsychiatric disorders and is an interesting target for drug development. Each su…
View article: Simultaneous 5-HT1BR agonist/5-HT6R antagonist action as a potential treatment of Parkinson’s disease and its comorbidities
Simultaneous 5-HT1BR agonist/5-HT6R antagonist action as a potential treatment of Parkinson’s disease and its comorbidities Open
Parkinson's disease (PD) treatment focuses mainly on the augmentation of dopamine transmission, but to alleviate adverse motor effects accompanying L-DOPA use, additional treatments with serotonergic (5-HT) medications may be considered. W…
View article: Design and Synthesis of Potential Multi-Target Antidepressants: Exploration of 1-(4-(7-Azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1H-indol-3-yl)pyrrolidine-2,5-dione Derivatives with Affinity for the Serotonin Transporter
Design and Synthesis of Potential Multi-Target Antidepressants: Exploration of 1-(4-(7-Azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1H-indol-3-yl)pyrrolidine-2,5-dione Derivatives with Affinity for the Serotonin Transporter Open
We describe the design, synthesis and structure–activity relationship of a novel series of 1-(4-(7-azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with combined effects on the serotonin (5-HT1A) …
View article: Contilisant+Tubastatin A Hybrids: Polyfunctionalized Indole Derivatives as New HDAC Inhibitor-Based Multitarget Small Molecules with <i>In Vitro</i> and <i>In Vivo</i> Activity in Neurodegenerative Diseases
Contilisant+Tubastatin A Hybrids: Polyfunctionalized Indole Derivatives as New HDAC Inhibitor-Based Multitarget Small Molecules with <i>In Vitro</i> and <i>In Vivo</i> Activity in Neurodegenerative Diseases Open
Herein, we describe the design, synthesis, and biological evaluation of 15 Contilisant+Tubastatin A hybrids. These ligands are polyfunctionalized indole derivatives developed by juxtaposing selected pharmacophoric moieties of…
View article: Unlocking the potential of higher-molecular-weight 5-HT7R ligands: Synthesis, affinity, and ADMET examination
Unlocking the potential of higher-molecular-weight 5-HT7R ligands: Synthesis, affinity, and ADMET examination Open
An increasing number of drugs introduced to the market and numerous repositories of compounds with confirmed activity have posed the need to revalidate the state-of-the-art rules that determine the ranges of properties the compounds should…
View article: Correction to: Unraveling psilocybin’s therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression
Correction to: Unraveling psilocybin’s therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression Open
View article: Uncovering the unique characteristics of different groups of 5-HT5AR ligands with reference to their interaction with the target protein
Uncovering the unique characteristics of different groups of 5-HT5AR ligands with reference to their interaction with the target protein Open
Background The serotonin 5-HT 5A receptor has attracted much more research attention, due to the therapeutic potential of its ligands being increasingly recognized, and the possibilities that lie ahead of these findings. There is a growing…
View article: Unraveling psilocybin’s therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression
Unraveling psilocybin’s therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression Open
View article: 5-HT6 receptor neutral antagonists protect astrocytes: A lesson from 2-phenylpyrrole derivatives
5-HT6 receptor neutral antagonists protect astrocytes: A lesson from 2-phenylpyrrole derivatives Open
View article: Physicochemical, structural and biological characterisation of poly(3-hydroxyoctanoate) supplemented with diclofenac acid conjugates — Harnessing the potential in the construction of materials for skin regeneration processes
Physicochemical, structural and biological characterisation of poly(3-hydroxyoctanoate) supplemented with diclofenac acid conjugates — Harnessing the potential in the construction of materials for skin regeneration processes Open
This study involved creating oligomeric conjugates of 3-hydroxy fatty acids and diclofenac, named Dic-oligo(3HAs). Advanced NMR techniques confirmed no free diclofenac in the mix. We tested diclofenac release under conditions resembling he…
View article: Exploring the molecular basis of treatment-resistant depression: Discoveries from a rat model and psilocybin therapy
Exploring the molecular basis of treatment-resistant depression: Discoveries from a rat model and psilocybin therapy Open
View article: 5-Ht6 Receptor Neutral Antagonists Protect Astrocytes a Lesson from 2-Phenylpyrrole Derivatives
5-Ht6 Receptor Neutral Antagonists Protect Astrocytes a Lesson from 2-Phenylpyrrole Derivatives Open
View article: Superiority of the Triple-Acting 5-HT<sub>6</sub>R/5-HT<sub>3</sub>R Antagonist and MAO-B Reversible Inhibitor <b>PZ-1922</b> over 5-HT<sub>6</sub>R Antagonist Intepirdine in Alleviation of Cognitive Deficits in Rats
Superiority of the Triple-Acting 5-HT<sub>6</sub>R/5-HT<sub>3</sub>R Antagonist and MAO-B Reversible Inhibitor <b>PZ-1922</b> over 5-HT<sub>6</sub>R Antagonist Intepirdine in Alleviation of Cognitive Deficits in Rats Open
The multifactorial origin and neurochemistry of Alzheimer's disease (AD) call for the development of multitarget treatment strategies. We report a first-in-class triple acting compound that targets serotonin type 6 and 3 receptors (5-HT-Rs…
View article: Synthesis and biological evaluation of novel 3-(5-substituted-1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with a dual affinity for serotonin 5-HT1A receptor and SERT
Synthesis and biological evaluation of novel 3-(5-substituted-1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with a dual affinity for serotonin 5-HT1A receptor and SERT Open
View article: Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats
Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats Open
View article: Novel object recognition test as an alternative approach to assessing the pharmacological profile of sigma-1 receptor ligands
Novel object recognition test as an alternative approach to assessing the pharmacological profile of sigma-1 receptor ligands Open
View article: Dual Piperidine-Based Histamine H<sub>3</sub> and Sigma-1 Receptor Ligands in the Treatment of Nociceptive and Neuropathic Pain
Dual Piperidine-Based Histamine H<sub>3</sub> and Sigma-1 Receptor Ligands in the Treatment of Nociceptive and Neuropathic Pain Open
In search of new dual-acting histamine H3/sigma-1 receptor ligands, we designed a series of compounds structurally based on highly active in vivo ligands previously studied and described by our team. However, we kept in m…
View article: Amisulpride as a potential disease‐modifying drug in the treatment of tauopathies
Amisulpride as a potential disease‐modifying drug in the treatment of tauopathies Open
INTRODUCTION Hyperphosphorylation and aggregation of the microtubule‐associated protein tau cause the development of tauopathies, such as Alzheimer's disease and frontotemporal dementia (FTD). We recently uncovered a causal link between co…
View article: Structure-Activity Relationships and Therapeutic Potential ofPurinergic P2X7 Receptor Antagonists
Structure-Activity Relationships and Therapeutic Potential ofPurinergic P2X7 Receptor Antagonists Open
The purinergic P2X7 receptor (P2X7R), an ATP-gated non-selective cation channel, has emerged as a gatekeeper of inflammation that controls the release of proinflammatory cytokines. As a key player in initiating the inflammatory signaling c…
View article: Gαi-derived peptide binds the µ-opioid receptor
Gαi-derived peptide binds the µ-opioid receptor Open
Background G protein-coupled receptors (GPCRs) transduce external stimuli into the cell by G proteins via an allosteric mechanism. Agonist binding to the receptor stimulates GDP/GTP exchange within the heterotrimeric G protein complex, whe…
View article: Impact of the Substitution Pattern at the Basic Center and Geometry of the Amine Fragment on 5-HT6 and D3R Affinity in the 1H-Pyrrolo[3,2-c]quinoline Series
Impact of the Substitution Pattern at the Basic Center and Geometry of the Amine Fragment on 5-HT6 and D3R Affinity in the 1H-Pyrrolo[3,2-c]quinoline Series Open
Salt bridge (SB, double-charge-assisted hydrogen bonds) formation is one of the strongest molecular non-covalent interactions in biological systems, including ligand–receptor complexes. In the case of G-protein-coupled receptors, such an i…
View article: Design and Synthesis of New Quinazolin-4-one Derivatives with Negative mGlu7 Receptor Modulation Activity and Antipsychotic-Like Properties
Design and Synthesis of New Quinazolin-4-one Derivatives with Negative mGlu7 Receptor Modulation Activity and Antipsychotic-Like Properties Open
Following the glutamatergic theory of schizophrenia and based on our previous study regarding the antipsychotic-like activity of mGlu7 NAMs, we synthesized a new compound library containing 103 members, which were examined for NAM mGlu7 ac…
View article: Structure, Mutagenesis, and QM:MM Modeling of 3-Ketosteroid Δ <sup>1</sup> -Dehydrogenase from <i>Sterolibacterium denitrificans</i> ─The Role of a New Putative Membrane-Associated Domain and Proton-Relay System in Catalysis
Structure, Mutagenesis, and QM:MM Modeling of 3-Ketosteroid Δ <sup>1</sup> -Dehydrogenase from <i>Sterolibacterium denitrificans</i> ─The Role of a New Putative Membrane-Associated Domain and Proton-Relay System in Catalysis Open
3-Ketosteroid Δ1-dehydrogenases (KstD) are important microbial flavin enzymes that initiate the metabolism of steroid ring A and find application in the synthesis of steroid drugs. We present a structure of the KstD from Ster…
View article: Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats
Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats Open
Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored topic concerns the use of repeated low doses of psychedelics, at a dose t…
View article: Isomeric Activity Cliffs—A Case Study for Fluorine Substitution of Aminergic G Protein-Coupled Receptor Ligands
Isomeric Activity Cliffs—A Case Study for Fluorine Substitution of Aminergic G Protein-Coupled Receptor Ligands Open
Currently, G protein-coupled receptors (GPCRs) constitute a significant group of membrane-bound receptors representing more than 30% of therapeutic targets. Fluorine is commonly used in designing highly active biological compounds, as evid…
View article: 1-(Arylsulfonyl-isoindol-2-yl)piperazines as 5-HT6R Antagonists: Mechanochemical Synthesis, In Vitro Pharmacological Properties and Glioprotective Activity
1-(Arylsulfonyl-isoindol-2-yl)piperazines as 5-HT6R Antagonists: Mechanochemical Synthesis, In Vitro Pharmacological Properties and Glioprotective Activity Open
In addition to the canonical Gs adenylyl cyclase pathway, the serotonin type 6 receptor (5-HT6R) recruits additional signaling pathways that control cognitive function, brain development, and synaptic plasticity in an agonist-dependent and…