283 results on '"Agata, Siwek"'
Search Results
202. SAR-studies on the importance of aromatic ring topologies in search for selective 5-HT7 receptor ligands among phenylpiperazine hydantoin derivatives
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Abrar Ashoor, Agata Siwek, Małgorzata Więcek, Andrzej J. Bojarski, Barbara Filipek, Katarzyna Kieć-Kononowicz, Jadwiga Handzlik, Katarzyna Kucwaj, Monika Kubacka, Bassem Sadek, and Grzegorz Satała
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Pharmacology ,Dose-Response Relationship, Drug ,Molecular Structure ,Hydrochloride ,Stereochemistry ,Hydantoins ,Organic Chemistry ,Phenylpiperazine ,General Medicine ,Alkylation ,Ligands ,Affinities ,Piperazines ,chemistry.chemical_compound ,Structure-Activity Relationship ,chemistry ,Receptors, Serotonin ,Drug Discovery ,Humans ,Mitsunobu reaction ,Selectivity ,Receptor ,5-HT receptor - Abstract
The current study is focused on newly developed phenylpiperazine derivatives of aromatic methylhydantoin differing in mutual positions of methyl and phenyl moieties. The new compounds were synthesized using Bucherer–Bergs reaction, two-phase alkylation, Mitsunobu reaction and/or an alkylation under microwave irradiation. The compounds developed were assessed on their affinity for serotoninergic receptors 5-HT1A, 5-HT6, 5-HT7 and α1-ARs in radioligand binding assays. Selected compounds were tested on their inhibitory effect at human 5-HT3A expressed in Xenopus Oocytes as well as on their activity at α1-adrenoceptor subtypes in functional and electrophysiological bioassays, respectively. Most of investigated compounds exhibited affinities for α1-ARs, 5-HT1A, 5-HT7 (Ki ∼ 0.8–353 nM) significantly higher than those for 5-HT6 receptors. Very weak inhibitory effect at 5-HT3A accompanied with high activity at α1D-AR subtypes were observed for selected representative compounds. Among the current series, particularly 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione hydrochloride (25a) displayed the highest 5-HT7 affinity with Ki = 3 nM and selectivity with 40–3600 fold towards 5-HT1A, 5-HT6, and α1-ARs.
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- 2014
203. Binding modes of DL-2-haloacid dehalogenase revealed by crystallography, modeling and isotope effects studies
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Piotr Paneth, Keiji Jitsumori, Tatsuo Kurihara, Rie Omi, Agata Siwek, Nobuyoshi Esaki, and Ken Hirotsu
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Stereochemistry ,Hydrolases ,Biophysics ,chemistry.chemical_element ,Crystallography, X-Ray ,Biochemistry ,Isotopes ,Catalytic Domain ,Kinetic isotope effect ,polycyclic compounds ,Chlorine ,Organic chemistry ,Enzyme Inhibitors ,Molecular Biology ,Dehalogenase ,chemistry.chemical_classification ,biology ,Isotopes of chlorine ,Substrate (chemistry) ,Active site ,Halogenation ,Stereoisomerism ,Molecular Docking Simulation ,Enzyme ,chemistry ,Mutation ,biology.protein ,Mutagenesis, Site-Directed ,Propionates ,Protein Binding - Abstract
Several pathways of biotic dechlorination can be found in enzymes, each characterized by different chlorine isotopic fractionation, which can thus serve as a signature of a particular mechanism. Unlike other dehalogenases, DL-2-haloacid dehalogenase, DL-DEX, converts both enantiomers of the substrate. Chlorine isotope effects for this enzyme are larger than in the case of other dehalogenases. Recently, the 3D structure of this enzyme became available and enabled us to model these isotope effects and seek their origin. We show that the elevated values of the chlorine kinetic isotope effects originate in part in the processes of binding and migration within the enzyme active site that precede the dehalogenation step.
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- 2013
204. Zinc as a marker of affective disorders
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Gabriel Nowak, Agata Siwek, Dominika Dudek, Magdalena Sowa-Kućma, Bartłomiej Pochwat, Leszek Witkowski, Marcin Siwek, Krzysztof Styczeń, Katarzyna Młyniec, and Bernadeta Szewczyk
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Pharmacology ,Mood Disorders ,Decreased Concentration ,chemistry.chemical_element ,General Medicine ,Zinc ,Bioinformatics ,medicine.disease_cause ,Pathophysiology ,Oxidative Stress ,Pharmacotherapy ,chemistry ,medicine ,Animals ,Humans ,State marker ,Psychology ,Depression (differential diagnoses) ,Oxidative stress ,Biomarkers ,Clinical psychology ,Immune activation - Abstract
Depression is considered as a chronic and recurring illness with functional impairment, significant disability, morbidity and mortality. Despite the extensive research carried out on depression, its pathophysiology is still poorly understood. An important problem concerning research into depressive disorder is the lack of biological markers which could improve diagnosis or indicate a risk of developing depression or risk of relapse. Several reports indicated decreased zinc concentrations and even its deficit in clinical depression, so the measurement of the concentration of this element in the blood of patients was suggested as a useful and specific clinical marker of depression. The reported results indicated that the serum zinc level might be a marker of depression as a state (state marker) in treatment responsive patients. However, in drug-resistant depression a decreased concentration of zinc may be a marker of traits (trait marker). It seems, however, that the measurement of the concentrations of zinc might be in the future a component of the battery of tests; of markers of immune activation and oxidative stress rather than itself alone.
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- 2013
205. Synthesis, in vitro biological screening and molecular docking studies of novel camphor-based thiazoles
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Eugenia Gospodarek, Tomasz Plech, Krzysztof Z. Laczkowski, Konrad Misiura, Emilia Ciok-Pater, Anna Biernasiuk, Krzysztof Skowron, Agata Siwek, and Anna Malm
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Antifungal Agents ,Stereochemistry ,Microbial Sensitivity Tests ,Biology ,Gram-Positive Bacteria ,Ligands ,Fungal Proteins ,Camphor ,chemistry.chemical_compound ,Bacterial Proteins ,Drug Discovery ,medicine ,Candida ,Binding Sites ,Molecular Structure ,Ligand (biochemistry) ,biology.organism_classification ,Yeast ,In vitro ,Anti-Bacterial Agents ,Ciprofloxacin ,Molecular Docking Simulation ,Thiazoles ,Biochemistry ,Cereus ,chemistry ,Fluconazole ,Bacteria ,medicine.drug - Abstract
Synthesis, characterization and investigation of antibacterial and antifungal activities of twelve camphor based 2,4-disubstituted 1,3-thiazoles is presented. Their structures were determined using NMR, IR, FAB MS and HRMS analyses. Among the derivatives, 3i and 5 were found to exhibit antifungal and antibacterial activities comparable to that of fluconazole and ciprofloxacin against yeast belonging to Candida spp., MIC 0.12-0.98 μg/ml and Gram-positive bacteria including both pathogenic S. aureus and opportunistic S. epidermidis, MIC 0.98-7.81 μg/ml, B. subtilis and B. cereus, MIC 3.91-31.25 μ g/ml, and M. luteus, MIC 0.98 μ g/ml species, respectively. Molecular docking studies of all compounds into the active sites of microbial enzymes indicated a possible targets SAP and NMT, thiazoles 3a-j, 4, 5 showed more favourable affinity than the native ligand.
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- 2013
206. Synthesis and pharmacological evaluation of novel tricyclic[2,1-f]theophylline derivatives
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Agnieszka, Zagórska, Maciej, Pawłowski, Agata, Siwek, Grzegorz, Kazek, Anna, Partyka, Dagmara, Wróbel, Magdalena, Jastrzębska-Więsek, and Anna, Wesołowska
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Male ,Behavior, Animal ,Molecular Structure ,Antidepressive Agents, Tricyclic ,Motor Activity ,Serotonin 5-HT1 Receptor Agonists ,Serotonin 5-HT1 Receptor Antagonists ,Receptors, Dopamine ,Dopamine D2 Receptor Antagonists ,Mice ,Structure-Activity Relationship ,Theophylline ,Receptors, Serotonin ,Serotonin 5-HT2 Receptor Antagonists ,Animals ,Rats, Wistar ,Antipsychotic Agents ,Body Temperature Regulation - Abstract
The multireceptor strategy was implemented to obtain potential antipsychotics and/or antidepressants in a series of long-chain arylpiperazines bearing a tricyclic theophylline fragment. Their binding profile toward monoaminergic receptors (α1, 5-HT(1A), 5-HT(2A), 5-HT6, 5-HT7, D2, D3) was determined as well. The selected compounds 7 and 9 were tested in functional in vivo models and showed, like atypical antipsychotic drugs, presynaptic 5-HT(1A) receptor agonistic and postsynaptic 5-HT(1A), 5-HT(2A), and D2 receptor antagonistic activity.
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- 2013
207. 7-3-Chlorophenypiperazinylalkyl derivatives of 8-alkoxy-purine-2,6-dione as a serotonin receptor ligands with potential antidepressant activity
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Małgorzata Zygmunt, Grażyna Chłoń-Rzepa, Agata Siwek, Maciej Pawłowski, Jacek Sapa, Gabriel Nowak, and Agnieszka Zagórska
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Purine ,Male ,Adrenergic receptor ,Stereochemistry ,Pharmacology ,Motor Activity ,Serotonergic ,Ligands ,Piperazines ,chemistry.chemical_compound ,Mice ,Animals ,Receptor, Serotonin, 5-HT2A ,Receptor ,5-HT receptor ,Swimming ,Behavior, Animal ,General Medicine ,Antidepressive Agents ,chemistry ,Purines ,Receptor, Serotonin, 5-HT1A ,Alkoxy group ,Antidepressant ,Serotonin Antagonists ,Behavioural despair test - Abstract
Background The previous study showed that arylpiperazine can condition affinity to α-adrenoceptors, 5-HT 1A /5-HT 2A receptors and compounds with arylpiperazine had antidepressant-like effect. The aim of this study was to determine the antidepressant-like activity of new arylpiperazines containing novel 8-alkoxy-purine-2,6-dione fragments. Methods New 3-chloroarylpiperazinylalkyl analogs of 8-alkoxy-purine-2,6-dione and their purine-2,6,8-trione analogs ( 2 – 5 ) were tested for their α 1 , α 2 , 5-HT 1A ,5-HT 2A , and 5-HT 7 receptor affinities in radioreceptor binding study. Moreover, in search for potential antidepressant properties of these compounds, the forced swim test in mice was conducted. Results Compounds 2 and 3 were potent 5-HT 1A receptor ligands with K i within the range on 12–15 nM. All investigated compounds were found to be highly active 5-HT 2A receptor ( K i 15–28 nM) and α 1 adrenoceptor ( K i 21–89 nM) ligands. In the forced swim test all the compounds showed a significantly activity in spite of their reducing ability of locomotor activity. The most potent effect was produced by compound 4 and 5 , which reduced the immobility time in this test in all used doses. Conclusion In our study the most potent antidepressant-like activity was produced by compounds 4 and 5 , which are selective for the 5-HT 2A and α 1 receptors.
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- 2013
208. Synthesis and evaluation of pharmacological properties of some new xanthone derivatives with piperazine moiety
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Natalia Szkaradek, Andrzej J. Bojarski, Anna M. Waszkielewicz, Agnieszka Gunia, Karolina Pytka, Henryk Marona, Edward Szneler, Agata Siwek, and Grzegorz Satała
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Stereochemistry ,Hydrochloride ,medicine.medical_treatment ,Xanthones ,Clinical Biochemistry ,5-HT ,Drug Evaluation, Preclinical ,Pharmaceutical Science ,Administration, Oral ,Biochemistry ,Piperazines ,1,4-piperazine derivatives ,chemistry.chemical_compound ,Seizures ,Drug Discovery ,Xanthone ,medicine ,Moiety ,Animals ,Receptor ,Molecular Biology ,Piperazine ,5-HT receptor ,Electroshock ,Organic Chemistry ,serotoninergic receptors ,Bioavailability ,Rats ,Kinetics ,Anticonvulsant ,chemistry ,xanthone ,Receptors, Serotonin ,MES ,Receptor, Serotonin, 5-HT1A ,epilepsy ,Molecular Medicine ,Anticonvulsants ,anticonvulsant activity ,adrenergic receptors ,Half-Life ,Protein Binding - Abstract
A series of new xanthone derivatives with piperazine moiety [1–7] was synthesized and evaluated for their pharmacological properties. They were subject to binding assays for α1 and β1 adrenergic as well as 5-HT1A, 5-HT6 and 5-HT7b serotoninergic receptors. Five of the tested compounds were also evaluated for their anticonvulsant properties. The compound 3a 3-methoxy-5-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-9H-xanthen-9-one hydrochloride exhibited significantly higher affinity for serotoninergic 5-HT1A receptors (Ki = 24 nM) than other substances. In terms of anticonvulsant activity, 6-methoxy-2-{[4-(benzyl)piperazin-1-yl]methyl}-9H-xanthen-9-one (5) proved best properties. Its ED50 determined in maximal electroshock (MES) seizure assay was 105 mg/kg b.w. (rats, p.o.). Combining of xanthone with piperazine moiety resulted in obtaining of compounds with increased bioavailability after oral administration.
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- 2013
209. Endogenous progesterone and its cellular binding sites in wheat exposed to drought stress
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Michał Dziurka, Jana Oklešťková, Ondřej Novák, Ewa Pociecha, Maciej Kocurek, Anna Janeczko, and Agata Siwek
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Drought stress ,Cytoplasm ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Endogeny ,Biochemistry ,Endocrinology ,Cultivar ,Binding site ,Molecular Biology ,Progesterone ,Triticum ,Cell Nucleus ,Binding Sites ,biology ,fungi ,Cell Membrane ,food and beverages ,Cell Biology ,Metabolism ,biology.organism_classification ,Droughts ,Horticulture ,Agronomy ,Seedling ,Molecular Medicine ,Hormone - Abstract
Progesterone is a basic hormone that regulates the metabolism in mammals. The presence of this compound has also been found in certain plants. It is believed that progesterone can regulate growth processes and resistance to stress, however, its precise role in plants remains unknown. The research conducted in this study was aimed at analyzing the content of endogenous progesterone and its cellular binding sites in the leaves of spring wheat exposed to drought. Changes were studied in two cultivars of wheat – a cultivar sensitive to drought (Katoda) and tolerant cultivar (Monsun). Plants had undergone periodic droughts during the seedling stage or in the phase of heading. The occurrence of free progesterone as well as its conjugated forms was observed in wheat studied. The amount of progesterone ranged from 0.2 to 5.8 pmol g FW−1 and was dependent on the cultivar, age of the plants, stage of development and fluctuated as a result of the exposure to drought. Cv. Katoda responded to a water deficit by lowering the amount of progesterone and cv. Monsun by increasing its level. Progesterone in plants grown in limited water conditions occurred primarily in a free form. While in the optimal watering conditions, some of its pool was found in the form of conjugates. In the spring wheat the occurrence of binding sites for progesterone was detected in cell membranes, cytoplasm and nuclei in the range of 10–36 fmol/mg of protein. The wheat cultivars tested, Monsun and Katoda, differ in their concentration of cellular binding sites for progesterone. This number varied in the individual fractions during different stages of plant development and due to the effect of drought stress. The number of binding sites for progesterone located in the membrane fraction of seedlings and flag leaves increased significantly under drought in the cv. Katoda (35–46%), but did not change in the cv. Monsun. Whereas the number of cytoplasmic progesterone binding sites increased during the drought in the cv. Monsun (about 50%), they did not change in the cv. Katoda. Changes in the amount of progesterone and its binding sites in the cell under the influence of drought were then different depending on whether the cultivar was tolerant or sensitive to drought. The possibility of utilizing these changes as markers of drought resistance is discussed. The results obtained suggest that progesterone is a part of wheat response to stress factors (drought).
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- 2013
210. Synthesis and preliminary evaluation of pharmacological properties of some piperazine derivatives of xanthone
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Agata Siwek, Henryk Marona, Anna Rapacz, Barbara Filipek, Natalia Szkaradek, Marek T. Cegla, and Karolina Pytka
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Male ,Hydrochloride ,Xanthones ,Clinical Biochemistry ,Pharmaceutical Science ,Blood Pressure ,Propranolol ,Urapidil ,Pharmacology ,Biochemistry ,Piperazines ,chemistry.chemical_compound ,Heart Rate ,Drug Discovery ,Xanthone ,medicine ,Animals ,Rats, Wistar ,Piperazine ,Molecular Biology ,Carvedilol ,ED50 ,Organic Chemistry ,Arrhythmias, Cardiac ,Stereoisomerism ,Rats ,Receptors, Adrenergic ,Blood pressure ,chemistry ,Molecular Medicine ,Anti-Arrhythmia Agents ,Protein Binding ,medicine.drug - Abstract
A series of 9 piperazine derivatives of xanthone were synthesized and evaluated for cardiovascular activity. The following pharmacological experiments were conducted: the binding affinity for adrenoceptors, the influence on the normal electrocardiogram, the effect on the arterial blood pressure and prophylactic antiarrhythmic activity in adrenaline induced model of arrhythmia (rats, iv). Three compounds revealed nanomolar affinity for α1-adrenoceptor which was correlated with the strongest cardiovascular (antiarrhythmic and hypotensive) activity in animals’ models. The most promising compound was 4-(3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride (12) which revealed antiarrhythmic activity with ED50 value of 0.69 mg/kg in adrenaline induced arrhythmia (rats, iv). Other synthesized xanthone derivatives, that is, (R,S)-4-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride (10) and (R,S)-4-(2-acetoxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride (11) also acted as potential antiarrhythmics in adrenaline induced model of arrhythmia in rats after intravenous injection (ED50 = 0.88 mg/kg and 0.89 mg/kg, respectively). These values were lower than values obtained for reference drugs such as propranolol and urapidil, but not carvedilol. Results were quite promising and suggested that in the group of xanthone derivatives new potential antiarrhythmics and hypotensives might be found.
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- 2013
211. Synthesis and biological evaluation of novel pyrrolidine-2,5-dione derivatives as potential antidepressant agents. Part 1
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Katarzyna Stachowicz, Andrzej J. Bojarski, Jadwiga Turło, Bernadeta Szewczyk, Małgorzata Wolak, Agata Siwek, Franciszek Pluciński, Jerzy Kleps, Gabriel Nowak, Andrzej Chodkowski, Anna Sławińska, Martyna Z. Wróbel, Andrzej Mazurek, Franciszek Herold, Grzegorz Satała, Aleksander P. Mazurek, and Anna Gomółka
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Male ,Models, Molecular ,Spectrometry, Mass, Electrospray Ionization ,Indoles ,Magnetic Resonance Spectroscopy ,Pyrrolidines ,Stereochemistry ,Motor Activity ,Ligands ,Binding, Competitive ,Pyrrolidine ,Body Temperature ,Mice ,Radioligand Assay ,chemistry.chemical_compound ,Serotonin Agents ,Drug Discovery ,Animals ,Humans ,Receptor, Serotonin, 5-HT2A ,Receptor ,Swimming ,5-HT receptor ,Serotonin transporter ,Serotonin Plasma Membrane Transport Proteins ,Pharmacology ,Molecular Structure ,biology ,Organic Chemistry ,Brain ,Biological activity ,General Medicine ,Nuclear magnetic resonance spectroscopy ,Carbon-13 NMR ,Combinatorial chemistry ,Antidepressive Agents ,Pyrrolidinones ,Protein Structure, Tertiary ,Rats ,HEK293 Cells ,Models, Chemical ,chemistry ,Docking (molecular) ,Receptor, Serotonin, 5-HT1A ,biology.protein - Abstract
A series of 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives was synthesized and their biological activity was evaluated. The chemical structures of the newly prepared compounds were confirmed by 1H NMR, 13C NMR and ESI-HRMS spectra data. All tested compounds proved to be potent 5-HT1A receptor and serotonin transporter protein (SERT) ligands. Among them, compounds 15, 18, 19 and 30 showed significant affinity for 5-HT1A and SERT. Computer docking simulations carried out for compounds 15, 31 and 32 to models of 5-HT1A receptor and SERT confirm the results of biological tests. Due to high affinity for the 5-HT1A receptor and moderate affinity for SERT, compounds 31, 32, 35, and 37 were evaluated for their affinity for D2L, 5-HT6, 5-HT7 and 5-HT2A receptors. In vivo tests, in turn, resulted in determining the functional activity of compounds 15, 18, 19 and 30 to the 5-HT1A receptor. The results of these tests indicate that all of the ligands possess properties characteristic of 5-HT1A receptor agonists.
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- 2013
212. Synthesis, antidepressant evaluation and docking studies of long-chain alkylnitroquipazines as serotonin transporter inhibitors
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Gabriel Nowak, Lech Kozerski, Agata Siwek, Aina Westrheim Ravna, Katarzyna Stachowicz, Andrzej J. Bojarski, Małgorzata Wolak, Ingebrigt Sylte, Jerzy Sitkowski, Irina Kufareva, Zdzisław Chilmonczyk, Karol Wolosewicz, Ruben Abagyan, Mari Gabrielsen, Elżbieta Bednarek, Wojciech Bocian, Anna Zawadzka, and Jerzy Kossakowski
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Male ,Stereochemistry ,Motor Activity ,Biochemistry ,Article ,Mice ,Drug Discovery ,Radioligand ,medicine ,Animals ,Binding site ,Serotonin Uptake Inhibitors ,Serotonin transporter ,Serotonin Plasma Membrane Transport Proteins ,Pharmacology ,Binding Sites ,biology ,Chemistry ,Quipazine ,Organic Chemistry ,Antidepressive Agents ,Protein Structure, Tertiary ,Molecular Docking Simulation ,Docking (molecular) ,Receptor, Serotonin, 5-HT1A ,biology.protein ,Molecular Medicine ,Antidepressant ,Selective Serotonin Reuptake Inhibitors ,Protein Binding ,medicine.drug - Abstract
Twelve alkyl analogues (1 - 12) of the high-affinity serotonin transporter (SERT) inhibitor 6-nitroquipazine (6-NQ) were synthesised and studied using in vitro radioligand competition binding assays to determine their binding affinity (Ki). The putative antidepressant activity of five of the binders with the highest SERT binding affinities was studied by the forced swim and locomotor activity mouse tests. The three dimensional (3D) structures of 8 and 9 were determined using NOE NMR technique. Flexible docking of the compounds was undertaken to illustrate the binding of the compounds in the SERT model. Our results showed that several of the 6-NQ analogues are high-affinity SERT inhibitors and indicated that the octyl (8), decyl (10) and dodecyl (12) 6-NQ analogues exhibit moderate antidepressant activity.
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- 2013
213. Involvement of NMDA and AMPA receptors in the antidepressant-like activity of antidepressant drugs in the forced swim test
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Piotr Popik, Agata Siwek, Ewa Poleszak, Bernadeta Szewczyk, Andrzej Pilc, Małgorzata Wolak, and Gabriel Nowak
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Cyclopropanes ,Male ,Imipramine ,N-Methylaspartate ,Morpholines ,AMPA receptor ,Citalopram ,Motor Activity ,Pharmacology ,Receptors, N-Methyl-D-Aspartate ,Mice ,Reboxetine ,chemistry.chemical_compound ,Quinoxalines ,Milnacipran ,Oxazines ,medicine ,Animals ,Escitalopram ,Receptors, AMPA ,business.industry ,Immobility Response, Tonic ,General Medicine ,Antidepressive Agents ,2-Amino-5-phosphonovalerate ,chemistry ,Antidepressant ,NBQX ,business ,Behavioural despair test ,medicine.drug - Abstract
Background The involvement of glutamate system (particularly the NMDAand AMPAreceptors) in the mechanism of antidepressant activity was demonstrated in preclinical and clinical studies. Methods In the present study, we investigated the effect of NMDAand AMPAreceptors’ ligands (agonists and antagonists) on the antidepressant-like activity of escitalopram, milnacipran, imipramine and reboxetine in the forced swim test in mice. Results Antidepressant activity (reduction in immobility time) of escitalopram and milnacipran but not of imipramine and reboxetine was antagonized by N-methyl-D-aspartate acid. CGP37849 (antagonist of the NMDAreceptor) enhanced the antidepressant activity of all examined antidepressants. On the other hand, CX614 (a potentiator/positive allosteric modulator of the AMPAreceptor) enhanced the antidepressant activity of imipramine and reboxetine but not of escitalopram and milnacipran in this test. NBQX (the AMPA receptor antagonist) did not influence the antidepressant activity of all tested agents. Conclusions The data indicate the complex interactions following the activation or blockade of theNMDAandAMPAreceptors with antidepressant drugs. The general phenomenon is the enhancing effect of the NMDAreceptor antagonism on the antidepressant activity. Moreover, is can be concluded that the activity of antidepressants with a serotonergic mechanism of action can be inhibited by NMDA activation, while antidepressants with a noradrenergic mechanism of action are dependent on AMPA receptor transmission.
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- 2013
214. Effect of Formononetin on Mechanical Properties and Chemical Composition of Bones in Rats with Ovariectomy-Induced Osteoporosis
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Maria Zych, Ilona Kaczmarczyk-Sedlak, Ewa Ozimina-Kamińska, Joanna Taranowicz, Agata Siwek, and Weronika Wojnar
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medicine.medical_specialty ,Pueraria ,biology ,Traditional medicine ,Article Subject ,business.industry ,Osteoporosis ,lcsh:Other systems of medicine ,biology.organism_classification ,medicine.disease ,lcsh:RZ201-999 ,Organic fraction ,chemistry.chemical_compound ,Astragalus ,Endocrinology ,Complementary and alternative medicine ,chemistry ,Internal medicine ,Ovariectomized rat ,medicine ,Glycyrrhiza ,Formononetin ,business ,Chemical composition ,Research Article - Abstract
Formononetin is a naturally occurring isoflavone, which can be found in low concentrations in many dietary products, but the greatest sources of this substance areAstragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra,andPueraria lobata, which all belong to Fabaceae family. Due to its structural similarity to 17β-estradiol, it can mimic estradiol’s effect and therefore is considered as a “phytoestrogen.” The aim of this study was to examine the effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. 12-week-old female rats were divided into 4 groups: sham-operated, ovariectomized, ovariectomized treated with estradiol (0.2 mg/kg) and ovariectomized treated with formononetin (10 mg/kg). Analyzed substances were administered orally for 4 weeks. Ovariectomy caused osteoporotic changes, which can be observed in bone biomechanical features (decrease of maximum load and fracture load and increase of displacements for maximum and fracture loads) and bone chemical composition (increase of water and organic fraction content, while a decrease of minerals takes place). Supplementation with formononetin resulted in slightly enhanced bone mechanical properties and bone chemistry improvement (significantly lower water content and insignificantly higher mineral fraction content). To summarize, administration of formononetin to ovariectomized rats shows beneficial effect on bone biomechanical features and chemistry; thus, it can prevent osteoporosis development.
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- 2013
215. Studies on novel pyridine and 2-pyridone derivatives of N-arylpiperazine as α-adrenoceptor ligands
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Marzena, Baran, Elzbieta, Kepczyńska, Marek, Zylewski, Agata, Siwek, Marek, Bednarski, and Marek Tadeusz, Cegła
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Male ,Structure-Activity Relationship ,Dose-Response Relationship, Drug ,Molecular Structure ,Pyridines ,Pyridones ,Receptors, Adrenergic, alpha-1 ,Adrenergic alpha-1 Receptor Antagonists ,Animals ,Rats, Wistar ,Ligands ,Piperazines ,Rats - Abstract
This paper describes the synthesis of a series of new N-arylpiperazine derivatives of pyridine and 2-pyridone. The in vitro pharmacological study indicated that all of the compounds possess affinity towards α1-adrenoceptors, with exception of 6d, and are selective over α2 receptor. The most potent compound 5f displayed 62-fold α2/α1 selectivity with Ki value of 27.3 nM for α1 receptor. Selectivity of other ligands ranged from 6 to more than 146-fold. Hydrochlorides of selected compounds with the best α1-adrenoceptor affinity (7b, 7e, 7f, 8b) were tested in vivo (hypotensive activity test in rats) and the results proved their α-adrenoreceptor antagonistic activity. Furthermore, the lipophilicity of the investigated compounds has been assessed experimentally and in silico.
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- 2012
216. Ionic liquids as surfactants in micellar liquid chromatography
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Jolanta, Flieger, Agata, Siwek, Magdalena, Pizoń, and Anna, Czajkowska-Żelazko
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Surface-Active Agents ,Ionic Liquids ,Chromatography, High Pressure Liquid ,Micelles - Abstract
This paper is devoted to application of ionic liquids as surfactants in LC of organic compounds, derivatives of 1,4-thiosemicarbazides. According to HPLC requirements the most advantageous conditions such as transparency for ultraviolet light, low CMC, additional inorganic salt additives, and appropriate organic solvent were established. The CMC was determined using conductivity measurements. Suitability of two different stationary phases: RP-C18 and cyanopropyl bonded phase was examined under micellar conditions. Chosen ionic liquid surfactant was compared to common traditional amphiphilic reagent - SDS. Elaborated on chromatographic micellar conditions were tested as a pilot technique for prediction of distribution coefficients of organic analytes in ionic liquid-based aqueous two-phase system.
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- 2012
217. Antidepressant and antipsychotic activity of new quinoline- and isoquinoline-sulfonamide analogs of aripiprazole targeting serotonin 5-HT₁A/5-HT₂A/5-HT₇ and dopamine D₂/D₃ receptors
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Paweł, Zajdel, Krzysztof, Marciniec, Andrzej, Maślankiewicz, Katarzyna, Grychowska, Grzegorz, Satała, Beata, Duszyńska, Tomasz, Lenda, Agata, Siwek, Gabriel, Nowak, Anna, Partyka, Dagmara, Wróbel, Magdalena, Jastrzębska-Więsek, Andrzej J, Bojarski, Anna, Wesołowska, and Maciej, Pawłowski
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Sulfonamides ,Behavior, Animal ,Dose-Response Relationship, Drug ,Molecular Structure ,Receptors, Dopamine D2 ,Aripiprazole ,Receptors, Dopamine D3 ,Motor Activity ,Quinolones ,Isoquinolines ,Antidepressive Agents ,Piperazines ,Dopamine D2 Receptor Antagonists ,Mice ,Structure-Activity Relationship ,Receptors, Serotonin ,Quinolines ,Animals ,Dizocilpine Maleate ,Antipsychotic Agents - Abstract
A series of new quinoline- and isoquinoline-sulfonamide analogs of aripiprazole was synthesized to explore the influence of two structural features - replacement of ether/amide moiety with sulfonamide one, and localization of a sulfonamide group in the azine moiety. In contrast to aripiprazole, compound 33 (N-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propyl)quinoline-7-sulfonamide) and 39 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)isoquinoline-3-sulfonamide) displaying multireceptor 5-HT(1A)/5-HT(2A)/5-HT(7)/D(2)/D(3) profile, and behaving as 5-HT(1A) agonists, D(2) partial agonists, and 5-HT(2A)/5-HT(7) antagonists, produced significant antidepressant activity in FST in mice. On the other hand, their 4-isoquinolinyl analog 40 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)isoquinoline-4-sulfonamide), with similar receptor binding and functional profile, additionally displayed remarkable antipsychotic properties in the MK-801-induced hyperlocomotor activity in mice.
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- 2012
218. Molecular properties prediction, docking studies, and antimicrobial screening of 1,3,4-thiadiazole and s-triazole derivatives
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Agata Siwek, Tomasz Plech, Pawel Staczek, Aleksandra Strzelczyk, and Joanna Stefańska
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Models, Molecular ,Cell Membrane Permeability ,Membrane permeability ,Biological Availability ,Biology ,beta-Lactamases ,Sterol 14-Demethylase ,Thiadiazoles ,Anti-Infective Agents ,Drug Discovery ,polycyclic compounds ,Humans ,chemistry.chemical_classification ,Chitinases ,General Medicine ,Triazoles ,Antimicrobial ,Combinatorial chemistry ,Sterol ,Bioavailability ,Enzyme ,Biochemistry ,chemistry ,Docking (molecular) ,Drug Design ,Molecular Medicine - Abstract
A series of 1,3,4-thiadiazoles and s-triazoles were subjected to Molinspiration, ALOGPS 2.1, and Osiris programs to predict their molecular properties that are important for drug candidates. Subsequently, all of them were docked into the active sites of enzymes namely glucosamine-6-phosphate synthase (GlcN-6-P), VIM-2 metallo-β- lactamase (VIM-2), chitinase A1 (ChiA1), and sterol 14 alpha-demethylase (CYP51) that were considered in antimicrobial studies of thiadiazole and s-triazole derivatives. Since all compounds fulfilled the criteria for good membrane permeability, oral bioavailability, low toxicity and the potential inhibitory activities towards VIM-2, ChiA1, and CYP51, most of them were synthesized and their antimicrobial activity has been tested.
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- 2012
219. ChemInform Abstract: Synthesis and Antimicrobial Evaluation of New 1-{[4-(4-Halogenophenyl)-4H-1,2,4-triazol-3-yl] sulfanyl}acetyl-4-substituted Thiosemicarbazides and Products of Their Cyclization
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Jakub Krol, Nazar Trotsko, Anna Malm, Monika Wujec, Agata Siwek, and Urszula Kosikowska
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chemistry.chemical_compound ,biology ,Chemistry ,Sulfanyl ,mental disorders ,Triazole derivatives ,Organic chemistry ,General Medicine ,Antimicrobial ,biology.organism_classification ,Combinatorial chemistry ,psychological phenomena and processes ,Bacteria - Abstract
The compounds (III) and (IV) are screened for their antimicrobial activity against Gram-positive and Gram-negative bacteria.
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- 2012
220. Synthesis and SAR-study for novel arylpiperazine derivatives of 5-arylidenehydantoin with α₁-adrenoceptor antagonistic properties
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Jadwiga, Handzlik, Ewa, Szymańska, Renata, Wójcik, Anna, Dela, Magdalena, Jastrzębska-Więsek, Janina, Karolak-Wojciechowska, Andrzej, Fruziński, Agata, Siwek, Barbara, Filipek, and Katarzyna, Kieć-Kononowicz
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Models, Molecular ,Structure-Activity Relationship ,Hydantoins ,Receptors, Adrenergic, alpha-1 ,Adrenergic alpha-1 Receptor Antagonists ,Molecular Conformation ,Animals ,Crystallography, X-Ray ,Piperazine ,Piperazines ,Rats - Abstract
The study is focused on a series of 5-arylidenehydantoin derivatives with a phenylpiperazine-hydroxypropyl fragment at N3 of the hydantoin ring. The compounds were assessed on their affinity for α(1)-adrenoceptors and evaluated in functional bioassays for their antagonistic properties. Crystal structures of (Z)-5-(4-chlorobenzylidene)-3-(3-(4-(2-ethoxyphenyl)piperazin-1-yl)-2-hydroxypropyl)imidazolidine-2,4-dione (7) and hydrochloride of (Z)-5-(4-chlorobenzylidene)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)imidazolidine-2,4-dione (10a) were solved using the X-ray diffraction method. Classical molecular mechanics (MMFFs force field, MCMM, MacroModel) were used to predict 3D structure of compounds 5a-18a using a crystal structure of 7. SAR analysis was performed on the basis of Barbaro's pharmacophore model and structural properties of previously investigated α(1)-adrenoceptor antagonists possessing a hydantoin fragment. Most of the compounds exhibited significant affinities for α(1)-ARs in nanomolar range (40-290 nM). The highest activities (K(i)75 nM) were observed for compounds possessing a 2-alkoxyphenylpiperazine fragment and two methoxy substituents at the benzylidene moiety. The results indicated that chemical properties, number and positions of substituents at the 5-arylidene fragment influenced the power of α(1)-affinities as follows: 3,4-di CH(3)O2,4-di CH(3)O4-Cl2,3-di CH(3)OH4-N(CH(3))(2).
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- 2012
221. Antifungal effect of 4-arylthiosemicarbazides against Candida species. Search for molecular basis of antifungal activity of thiosemicarbazide derivatives
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Agata Siwek, Katarzyna Dzitko, Joanna Stefańska, and Artur Ruszczak
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Antifungal Agents ,Molecular model ,Stereochemistry ,Cytotoxicity ,Static Electricity ,Molecular Conformation ,Microbial Sensitivity Tests ,Ligands ,Catalysis ,Cell Line ,Inorganic Chemistry ,chemistry.chemical_compound ,Mice ,Species Specificity ,Catalytic Domain ,Structure–activity relationship ,Animals ,Antifungal activity ,Isoquinoline ,Physical and Theoretical Chemistry ,Glutamine amidotransferase ,Candida ,chemistry.chemical_classification ,DNA ligase ,Original Paper ,biology ,Cell Death ,Ligand ,Topoisomerase ,Organic Chemistry ,Thiosemicarbazide derivative ,Structure-activity relationship ,Computer Science Applications ,Semicarbazides ,Molecular Docking Simulation ,Biochemistry ,chemistry ,Computational Theory and Mathematics ,Docking (molecular) ,Molecular docking ,biology.protein ,Thermodynamics ,Acyltransferases - Abstract
The in vitro antifungal potency of six series of 4-arylthiosemicarbazides was evaluated. Two isoquinoline derivatives with an ortho-methoxy or ortho-methyl group at the phenyl ring were the most potent antifungal agents. Molecular modeling studies and docking of all 4-arylthiosemicarbazides into the active sites of sterol 14α-demethylase (CYP51), topoisomerase II (topo II), l-glutamine: d-fructose-6-phosphate amidotransferase (GlcN-6-P), secreted aspartic proteinase (SAP), N-myristoyltransferase (NMT), and UDP-N-acetylmuramoyl-l-alanine:d-glutamate ligase (MurD) indicated the importance of both structural and electronic factors in ligand recognition and thus for the antifungal effectiveness of 4-arylthiosemicarbazides. A possible antifungal target was identified (NMT) and isoquinoline-thiosemicarbazides showed more favorable affinity than the native ligand. Figure Electrostatic potential surface of isoquiniline derivative compound 6o with antifungal activity Electronic supplementary material The online version of this article (doi:10.1007/s00894-012-1420-5) contains supplementary material, which is available to authorized users.
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- 2012
222. ChemInform Abstract: Synthesis, α-Adrenoceptors Affinity and α1-Adrenoceptor Antagonistic Properties of Some 1,4-Substituted Piperazine Derivatives
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M. Dybaia, Anna M. Waszkielewicz, T. Pociecha, Barbara Filipek, Henryk Marona, Agnieszka Gunia, Monika Kubacka, Agata Siwek, and Edward Szneler
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Piperazine ,chemistry.chemical_compound ,Chemistry ,Stereochemistry ,General Medicine ,α adrenoceptors ,α1 adrenoceptor - Abstract
A series of 1,4-substituted piperazine derivatives (I) are synthesized and evaluated for affinity towards α1- and α2-receptors by radioligand-binding assay.
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- 2012
223. Serotonin transporter activity of imidazolidine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives in aspect of their acid–base properties
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Maciej Pawłowski, Agata Siwek, Anna Czopek, Małgorzata Dybała, Gabriel Nowak, and Agnieszka Zagórska
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Purine ,Base (chemistry) ,Stereochemistry ,Potentiometric titration ,Imidazo[2,1-f]purine-2,4-dione ,Dissociation constant ,dissociation constant ,chemistry.chemical_compound ,Pharmacology, Toxicology and Pharmaceutics(all) ,Imidazolidine ,Imidazolidine-2,4-dione ,General Pharmacology, Toxicology and Pharmaceutics ,Serotonin transporter ,Original Research ,chemistry.chemical_classification ,biology ,Organic Chemistry ,serotonin transporter ,Affinities ,serotonin receptor 5-HT_{1A} ,chemistry ,imidazo[2,1-f]purine-2,4-dione ,Serotonin receptor 5-HT1A ,biology.protein ,imidazolidine-2,4-dione ,Experimental methods - Abstract
Affinities of arylpiperazinylalkyl derivatives of imidazo[2,1-f]purine-2,4-dione and imidazolidine-2,4-dione for serotonin transporter and their acid-base properties were evaluated. The dissociation constant (pK(a)) of compounds 1-22 were determinated by potentiometric titration and calculated using pKalc 3.1 module of the Pallas system. The data from experimental methods and computational calculations were compared and suitable conclusions were reached.
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- 2012
224. Synthesis and structure-activity relationship studies of 4-arylthiosemicarbazides as topoisomerase IV inhibitors with Gram-positive antibacterial activity. Search for molecular basis of antibacterial activity of thiosemicarbazides
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Agata Siwek, Joanna Stefańska, and Paweł Stączek
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DNA Topoisomerase IV ,Models, Molecular ,Staphylococcus aureus ,Molecular model ,Topoisomerase IV ,Stereochemistry ,Topoisomerase Inhibitors ,Molecular Conformation ,Chemistry Techniques, Synthetic ,Microbial Sensitivity Tests ,Gram-Positive Bacteria ,DNA gyrase ,Structure-Activity Relationship ,Drug Discovery ,Structure–activity relationship ,Pharmacology ,biology ,Chemistry ,Topoisomerase ,Organic Chemistry ,General Medicine ,biology.organism_classification ,Anti-Bacterial Agents ,Semicarbazides ,Biochemistry ,Docking (molecular) ,biology.protein ,Antibacterial activity ,Bacteria - Abstract
1-(indol-2-carbonyl)-4-(4-nitrophenyl)-thiosemicarbazide was synthesized and antibacterial and type IIA topoisomerases (DNA gyrase and topoisomerase IV) activity was evaluated. It was found that it shows activity against Gram-positive bacteria with MICs of 50 μg/mL and inhibitory action against topoisomerase IV with an IC(50) of 14 μM. Although modification of its structure resulted in molecules with a lower biological profile, our observations strongly implicate that thiosemicarbazide derivatives participate in at least two different mechanisms of antibacterial activity; one is connected with the inhibition of topoisomerase IV, while the nature of the other cannot be elucidated from the limited data collected thus far. The differences in bioactivity further investigated by the molecular modeling approach and docking studies suggest that inhibitory activity of 4-arylthiosemicarbazides is connected with electronic structure rather than the geometry of the molecule.
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- 2011
225. ChemInform Abstract: Synthesis and Antimicrobial Activity of Thiosemicarbazides, s-Triazoles and Their Mannich Bases Bearing 3-Chlorophenyl Moiety
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Anna Malm, Tomasz Plech, Monika Wujec, Urszula Kosikowska, and Agata Siwek
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Bearing (mechanical) ,Chemistry ,law ,Triazole derivatives ,Moiety ,General Medicine ,Antimicrobial ,Combinatorial chemistry ,law.invention - Abstract
A fast, facile, and efficient method for the preparation of title compounds (III) is described.
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- 2011
226. Problems with molecular mechanics implementations on the example of 4-benzoyl-1-(4-methyl-imidazol-5-yl)-carbonylthiosemicarbazide
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Agata Siwek, Katarzyna Świderek, and Stefan Jankowski
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Models, Molecular ,Chemistry ,Organic Chemistry ,Imidazoles ,Molecular Conformation ,Molecular mechanics ,Catalysis ,Computer Science Applications ,Anti-Bacterial Agents ,Semicarbazides ,Inorganic Chemistry ,Computational Theory and Mathematics ,Computational chemistry ,Methods ,Physical and Theoretical Chemistry ,Enzyme Inhibitors ,Antibacterial activity - Abstract
Results from force fields implemented in HyperChem, a program frequently used in studies of bioactive compounds, have been compared using the example of the conformational analysis of a 1-carbonylthiosemicarbazide that exhibits strong antibacterial activity. By comparing these results with the original force fields and the experimental NMR ROESY spectrum, it was shown that these implementations can lead to erroneous results.
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- 2011
227. Antimicrobial activity and SAR study of some novel thiosemicarbazide derivatives bearing piperidine moiety
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Agata Siwek and Joanna Stefańska
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Antifungal ,Models, Molecular ,Antifungal Agents ,Bacteria ,Dose-Response Relationship, Drug ,Molecular Structure ,medicine.drug_class ,Stereochemistry ,Chemistry ,Fungi ,Microbial Sensitivity Tests ,Antimicrobial ,Combinatorial chemistry ,Anti-Bacterial Agents ,Semicarbazides ,chemistry.chemical_compound ,Structure-Activity Relationship ,Piperidines ,Molecular descriptor ,Drug Discovery ,medicine ,Moiety ,Piperidine ,Hydration energy ,HOMO/LUMO - Abstract
In this study novel thiosemicarbazides bearing piperidine moiety were synthesized in order to investigate their possible antibacterial and antifungal activities. A structure-activity relationship (SAR) study including conformational analysis and some physicochemical descriptors was carried out to provide the guidance for further synthetic work. The significant molecular descriptors related to the compounds with antifungal activity were: electrostatic potential surface, the highest occupied molecular orbital energy, surface area, volume, and hydration energy.
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- 2011
228. ChemInform Abstract: Structure-Activity Relationship of s-Triazoles and Thiadiazoles as Analgesics
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Ewa Jagiełło-Wójtowicz, Edyta Kusmierz, Tomasz Plech, Agata Siwek, Monika Wujec, and Anna Chodkowska
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medicine.anatomical_structure ,Behavioral test ,Thiadiazoles ,Stereochemistry ,Chemistry ,Central nervous system ,medicine ,Triazole derivatives ,Structure–activity relationship ,General Medicine - Abstract
The influence of the title compounds on the central nervous system of mice in some behavioral tests is investigated.
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- 2010
229. ChemInform Abstract: Synthesis and in vitro Antibacterial Evaluation of 1-Substituted-4-ethoxycarbonylmethylthiosemicarbazides (III) and Products of Their Dehydrocyclization
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Monika Wujec, Agata Siwek, Irena Wawrzycka-Gorczyca, and Joanna Stefańska
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biology ,Chemistry ,mental disorders ,Triazole derivatives ,Potency ,Organic chemistry ,General Medicine ,biology.organism_classification ,Antibacterial activity ,In vitro ,Bacteria - Abstract
The synthesized compounds are screened for their antibacterial activity, but only three of the tested substances show weak potency against Gram-positive bacteria.
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- 2010
230. Synthesis and Adrenolytic Activity of New Propanolamines
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Agnieszka Nowak-Król, Marek Bednarski, Grażyna Groszek, Agnieszka Bis, Agata Siwek, Agata Bajek, and Barbara Filipek
- Subjects
Adrenergic Antagonists ,Magnetic Resonance Spectroscopy ,Epinephrine ,synthesis ,Stereochemistry ,Pharmaceutical Science ,Blood Pressure ,In Vitro Techniques ,Article ,Analytical Chemistry ,Propanolamines ,lcsh:QD241-441 ,Electrocardiography ,lcsh:Organic chemistry ,Ileum ,Drug Discovery ,Animals ,α1-andrenoceptor antagonist ,Physical and Theoretical Chemistry ,Molecular Structure ,Chemistry ,Organic Chemistry ,Antagonist ,Arrhythmias, Cardiac ,Nuclear magnetic resonance spectroscopy ,Adrenergic alpha-2 Receptor Antagonists ,Adrenergic beta-1 Receptor Antagonists ,Rats ,Chemistry (miscellaneous) ,Adrenergic alpha-1 Receptor Antagonists ,Lead structure ,Molecular Medicine ,Rabbits ,pharmacology ,Anti-Arrhythmia Agents - Abstract
The synthesis of (2 R,S )-1-(6-methoxy-4-(methoxymethyl)-1 H -indol-5-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and (2 R,S )-1-(4-methoxy-6-(methoxy-methyl)-1 H -indol-5-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol is described. The compounds were tested for electrographic, antiarrhythmic, hypotensive, and spasmolytic activity, as well as for α 1 -, α 2 - and β 1 -adrenoceptor binding affinity. Keywords: α 1 -andrenoceptor antagonist; synthesis; pharmacology 1. Introduction In our search for new aminopropan-2-ol derivatives with cardiovascular activity among, we obtained the compound (2 R,S )-1-(1 H -indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol, ( R,S )-9 (Figure 1) [1] which became a lead structure for further investigations. The compound ( R,S )-9 possesses α 1 - and β 1 -adrenolytic, antiarrhythmic, and hypotensive activities similar to carvedilol, which is a very effective compound in the treatment of such cardiovascular diseases as OPEN ACCESS
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- 2010
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231. Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT(1A) activity. part 3
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Aleksander P. Mazurek, Małgorzata Dybała, Jerzy Kleps, Andrzej Mazurek, Franciszek Herold, Jadwiga Turło, Maciej Dawidowski, Łukasz Izbicki, Agata Siwek, Franciszek Pluciński, Andrzej Chodkowski, Gabriel Nowak, and Katarzyna Stachowicz
- Subjects
Models, Molecular ,Pyrimidine ,Stereochemistry ,Protein Conformation ,Serotonin 5-HT1 Receptor Antagonists ,Chemical synthesis ,Body Temperature ,chemistry.chemical_compound ,Mice ,Structure-Activity Relationship ,Drug Discovery ,Structure–activity relationship ,Moiety ,Animals ,Pharmacology ,Bicyclic molecule ,Chemistry ,Organic Chemistry ,Biological activity ,General Medicine ,Serotonin 5-HT1 Receptor Agonists ,Radioligand Assay ,Rats ,Piperazine ,Pyrimidines ,Receptor, Serotonin, 5-HT1A ,Selective Serotonin Reuptake Inhibitors - Abstract
A series of novel 4-aryl-pyrido[1,2-c]pyrimidine derivatives containing a 1-(2-quinoline)piperazine moiety was synthesized. The chemical structure of new compounds was confirmed by FT-IR, (1)H NMR, (13)C NMR and HRMS spectra as well as elemental analysis. Affinity of the novel pyrido[1,2-c]pyrimidine derivatives for 5-HT1A, 5-HT2A receptors and serotonin transporter (SERT) was evaluated in an in vitro radioligand binding assay. Tested compounds showed moderate to high affinity for 5-HT1AR and SERT and low affinity for 5-HT2AR. Selected ligands were subjected to in vivo tests, such as induced hypothermia and the forced swimming test in mice, which determined presynaptic agonistic activity of the ligands 8d, 8e, 9d and 9e and presynaptic antagonistic activity of the ligands 8a, 8b, 9a, 9b. Additionally, metabolic stability evaluation was performed for selected ligands, proving that a para-substitution in the 4-aryl-pyrido[1,2-c]pyrimidine moiety leads to an increase in stability, whereas a substitution in the ortho-position lowers the stability.
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- 2010
232. Pharmacophore models based studies on the affinity and selectivity toward 5-HT1A with reference to α1-adrenergic receptors among arylpiperazine derivatives of phenytoin
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Agata Siwek, Barbara Filipek, Jarosław Handzlik, Szczepan Mogilski, Monika Kubacka, Ewa Szymańska, Krystyna Nędza, Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz
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Models, Molecular ,Stereochemistry ,Hydrochloride ,Clinical Biochemistry ,Pharmaceutical Science ,Hydantoin ,Phenylpiperazine ,Biochemistry ,Molecular mechanics ,chemistry.chemical_compound ,Radioligand Assay ,Structure-Activity Relationship ,Receptors, Adrenergic, alpha-1 ,Drug Discovery ,Animals ,Rats, Wistar ,Molecular Biology ,Alkyl ,chemistry.chemical_classification ,Hydantoins ,Organic Chemistry ,Affinities ,Rats ,chemistry ,Phenytoin ,Receptor, Serotonin, 5-HT1A ,Molecular Medicine ,Pharmacophore ,Selectivity - Abstract
The study is focused on (2-alkoxy)phenylpiperazine derivatives of 1-(2-hydroxy-3-(4-arylpiperazin-1-yl)propyl)-5,5-diphenylimidazolidine-2,4-dione with alkyl or ester substituents at N3 of hydantoin ring, as well as a new designed and synthesized series of compounds with a free N3H group or N3-acetic acid terminal fragment. The compounds were assessed on their affinity for 5-HT 1A and α 1 -adrenoceptors and evaluated in functional bioassays for antagonistic properties. Classical molecular mechanics (MMFFs force field, MCMM, MacroModel) and DFT methods (B3LYP functional, Gaussian 0.3) were used to investigate 3D structure of the compounds. SAR analysis was based on two pharmacophore models, the one described by Barbaro et al. for α 1 -adenoceptor antagonist and the model of Lepailleur et al. for 5-HT 1A receptor ligands. All compounds exhibited significant to moderate affinities for 5-HT 1A receptors in nanomolar range (7–610 nM). The highest activity (7 nM) and selectivity (17.38) for 5-HT 1A was observed for 1-(3-(4-(2-ethoxyphenyl)piperazin-1-yl)-2-hydroxypropyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione ( 13a ). Among new synthesized compounds 1-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5,5-diphenylimidazolidine-2,4-dione hydrochloride ( 20a ) displayed the highest affinity (16.6 nM) and selectivity (5.72) for α 1 -AR.
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- 2010
233. The involvement of NMDA and AMPA receptors in the mechanism of antidepressant-like action of zinc in the forced swim test
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Bernadeta Szewczyk, Piotr Wlaź, Andrzej Wróbel, Agnieszka Cichy, Krystyna Gołembiowska, Agata Siwek, Ewa Poleszak, Andrzej Pilc, Joanna Listos, Magdalena Sowa-Kućma, Małgorzata Dybała, Gabriel Nowak, and S. Słotwiński
- Subjects
Male ,N-Methylaspartate ,CGP-37849 ,Clinical Biochemistry ,AMPA receptor ,Pharmacology ,Motor Activity ,Biochemistry ,chemistry.chemical_compound ,Mice ,AMPA ,Animals ,Receptors, AMPA ,Rats, Wistar ,Receptor ,Swimming ,forced swim test ,antidepressant ,Depression ,Organic Chemistry ,zinc ,Antagonist ,Glutamate receptor ,Antidepressive Agents ,Rats ,Zinc ,chemistry ,NMDA ,glutamate receptors ,NMDA receptor ,NBQX ,human activities ,Behavioural despair test - Abstract
Antidepressant-like activity of zinc in the forced swim test (FST) was demonstrated previously. Enhancement of such activity by joint administration of zinc and antidepressants was also shown. However, mechanisms involved in this activity have not yet been established. The present study examined the involvement of the NMDA and AMPA receptors in zinc activity in the FST in mice and rats. Additionally, the influence of zinc on both glutamate and aspartate release in the rat brain was also determined. Zinc-induced antidepressant-like activity in the FST in both mice and rats was antagonized by N-methyl-D-aspartic acid (NMDA, 75 mg/kg, i.p.) administration. Moreover, low and ineffective doses of NMDA antagonists (CGP 37849, L-701,324, D-cycloserine, and MK-801) administered together with ineffective doses of zinc exhibit a significant reduction of immobility time in the FST. Additionally, we have demonstrated the reduction of immobility time by AMPA receptor potentiator, CX 614. The antidepressant-like activity of both CX 614 and zinc in the FST was abolished by NBQX (an antagonist of AMPA receptor, 10 mg/kg, i.p.), while the combined treatment of sub-effective doses of zinc and CX 614 significantly reduces the immobility time in the FST. The present study also demonstrated that zinc administration potentiated a veratridine-evoked glutamate and aspartate release in the rat's prefrontal cortex and hippocampus. The present study further suggests the antidepressant properties of zinc and indicates the involvement of the NMDA and AMPA glutamatergic receptors in this activity.
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- 2010
234. ChemInform Abstract: Novel 4-Aryl-pyrido[1,2-c]pyrimidines with Dual SSRI and 5-HT1AActivity. Part 1
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Lukasz Izbicki, Marek Król, Franciszek Herold, Agata Siwek, Jerzy Kleps, Małgorzata Dybała, Gabriel Nowak, Jadwiga Turło, Andrzej Chodkowski, and Katarzyna Stachowicz
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Agonist ,animal structures ,medicine.drug_class ,musculoskeletal, neural, and ocular physiology ,Aryl ,Antagonist ,General Medicine ,Pharmacology ,In vitro ,chemistry.chemical_compound ,nervous system ,chemistry ,In vivo ,Postsynaptic potential ,polycyclic compounds ,medicine ,heterocyclic compounds ,Receptor - Abstract
Synthesis, in vitro affinity for 5-HT1A receptors and SERT, SAR, and in vivo agonist/antagonist properties toward pre- and postsynaptic 5-HT1A receptors are described.
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- 2009
235. Zinc-induced adaptive changes in NMDA/glutamatergic and serotonergic receptors
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Bernadeta Szewczyk, Agnieszka Cichy, Ewa Poleszak, Lucyna Pomierny-Chamioło, Agata Siwek, Andrzej Pilc, Anna Piotrowska, Magdalena Sowa-Kućma, Gabriel Nowak, and Beata Legutko
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Male ,medicine.medical_specialty ,Glycine ,Serotonergic ,Hippocampus ,Receptors, N-Methyl-D-Aspartate ,Glutamatergic ,Radioligand Assay ,Neurotrophic factors ,Internal medicine ,medicine ,Animals ,Receptor, Serotonin, 5-HT2A ,RNA, Messenger ,Rats, Wistar ,Receptor ,5-HT receptor ,Pharmacology ,Aspartic Acid ,Chemistry ,Brain-Derived Neurotrophic Factor ,General Medicine ,Antidepressive Agents ,Frontal Lobe ,Rats ,Zinc ,Endocrinology ,Receptor, Serotonin, 5-HT1A ,Antidepressant ,NMDA receptor - Abstract
Preclinical data indicate the involvement of glutamatergic and serotonergic pathways in the antidepressant activity of zinc. The present study investigated alterations in N-methyl-D-aspartate (NMDA)/glutamatergic and serotonergic receptors (using radioligand binding) induced by chronic treatment (14-day) with zinc hydroaspartate (65 mg/kg). Moreover, the mRNA and protein levels of brain-derived neurotrophic factor (BDNF) were also assessed. Chronic zinc administration reduced the affinity of glycine to glycine/NMDA receptors in the rat frontal cortex and increased the density of 5-HT 1A and 5-HT 2A serotonin receptors in the hippo-campus and frontal cortex, respectively. These receptor alterations may be in part due to increased BDNF mRNA and protein levels in the rat frontal cortex. These results indicate that chronic zinc treatment alters glutamatergic and serotonergic systems, which is a hallmark of clinically effective antidepressants.
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- 2009
236. ChemInform Abstract: Synthesis and Theoretical Characterization of Some New 4-Substituted-1,3-diphenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazoles with Potential Pharmacological Activity
- Author
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Monika Wujec, Agata Siwek, Maria Dobosz, and Piotr Paneth
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Thiadiazoles ,Computational chemistry ,Chemistry ,Heteroatom ,Lipinski's rule of five ,Triazole derivatives ,Organic chemistry ,Biological activity ,General Medicine ,Tautomer - Abstract
Synthesis of some new triazoles fused to triazoles 5a–c or thiadiazoles 6a–c and the thiol-thione tautomeric equilibrium study of the title compounds are reported. The “rule of five” and complementary criteria of pharmacokinetic properties were determined to predict whether these compounds are orally bioavailable. Semiempirical parameterizations have been critically benchmarked for the thiol-thione tautomeric equilibrium against the DFT calculations. It was shown that unlike the AM1 and PM3 Hamiltonians, which erroneously predict higher stability of the thiol tautomer, the newly developed RM1 Hamiltonian, on the other hand, predicts energetics of this equilibrium in excellent agreement with the DFT results. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:713–718, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20499
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- 2009
237. Synthesis, lipophilicity and antimicrobial activity of new derivatives of thiosemicarbazides and 1,2,4-triazoline-5-thione
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Monika, Wujec, Joanna, Stefańska, Agata, Siwek, and Małgorzata, Tatarczak
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Bacteria, Aerobic ,Structure-Activity Relationship ,Anti-Infective Agents ,Fungi ,Thiones ,Triazoles ,Hydrophobic and Hydrophilic Interactions ,Semicarbazides - Abstract
In the reaction of hydrazide of 3,4-dimethoxyphenylacetic acid (1) with isothiocyanate the respective thiosemicarbazide derivatives (2) were obtained. Further cyclization with 2% NaOH led to the formation of 3-[(3,4-dimethoxyphenyl)methyl]-4-substituted-1,2,4-triazoline-5-thiones (3). The structures of all new products were confirmed by analytical and spectroscopic methods. All compounds were screened for their in vitro activity against some species of aerobic bacteria and fungi. The lipophilicity of the synthesized molecules was also studied.
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- 2009
238. Antidepressant-like effect of chromium chloride in the mouse forced swim test: involvement of glutamatergic and serotonergic receptors
- Author
-
Anna, Piotrowska, Katarzyna, Młyniec, Agata, Siwek, Małgorzata, Dybała, Włodzimierz, Opoka, Ewa, Poleszak, and Gabriel, Nowak
- Subjects
Male ,Mice ,Chlorides ,Depression ,Chromium Compounds ,Quinoxalines ,Receptors, Serotonin ,Ritanserin ,Animals ,Receptors, AMPA ,Receptors, N-Methyl-D-Aspartate ,Antidepressive Agents ,Swimming - Abstract
Chromium (Cr) (III), an essential microelement of living organisms, was reported to exhibit potential antidepressant properties in preclinical and clinical studies. The aim of the present study was to examine the effect of CrCl(3) ip administration in the forced swim test (FST) in mice and the involvement of glutamatergic and serotonergic receptors in the antidepressant-like activity of chromium. CrCl(3) in a dose of 12 mg/kg, but not in doses of 6 or 32 mg/kg, reduced the immobility time in the FST. The locomotor activity was reduced by CrCl(3) in a dose of 32 mg/kg. Moreover, the reduction of the immobility time induced by the active dose (12 mg/kg) of CrCl(3) was completely abolished by NBQX (10 mg/kg; an antagonist of the AMPA receptor) pretreatment and partially inhibited by ritanserin (4 mg/kg; an antagonist of 5-HT(2A/C) receptor), WAY 1006335 (0.1 mg/kg; an antagonist of 5-HT(1A) receptor) and N-methyl-D-aspartate (75 mg/kg; agonist of NMDA receptor) administration. The present study demonstrates the antidepressant-like activity of chromium in the mouse FST and indicates the major role of the AMPA receptor and participation of NMDA glutamatergic and 5-HT(1) and 5-HT(2A/C) serotonin receptors in this activity.
- Published
- 2008
239. Influence of the solvent description on the predicted mechanism of SN2 reactions
- Author
-
Joanna Dzierzawska, Michal Rostkowski, Monika Wujec, Rafał Kamiński, Agata Siwek, and Piotr Paneth
- Subjects
Aqueous solution ,Chemistry ,Thermodynamics ,Water ,Acetates ,Triazoles ,Transition state ,Surfaces, Coatings and Films ,Hydrocarbons, Brominated ,Solvent ,Ethyl bromoacetate ,chemistry.chemical_compound ,Kinetics ,Reaction rate constant ,Blood serum ,Models, Chemical ,Materials Chemistry ,Solvents ,SN2 reaction ,Organic chemistry ,Physical and Theoretical Chemistry ,Solvent effects - Abstract
The influence of the implicit solvent model on transition state structures of two S N2 reactions of biochemical importance is presented. In the considered methyl transfer reaction, we show experimentally that the rate constant in blood serum is about 60% slower than in the aqueous solution and that the implicit solvent model with slightly modified parameters for water captures correctly the energetics of this reaction. With the example of the reaction between 4-methyl-1,2,4-triazol-3-thione and ethyl bromoacetate, we show that relative stabilities of the conformationally different transition states depend upon the solvent inclusion strategy.
- Published
- 2008
240. The involvement of serotonergic system in the antidepressant effect of zinc in the forced swim test
- Author
-
Piotr Wlaź, Gabriel Nowak, Lucyna Pomierny-Chamioło, Andrzej Wróbel, Małgorzata Dybała, Anna Piotrowska, Ewa Poleszak, Agata Siwek, Bernadeta Szewczyk, Piotr Brański, Agnieszka Cichy, Eliza Blicharska, and Andrzej Pilc
- Subjects
Male ,medicine.medical_specialty ,Serotonin ,Pyridines ,Morpholines ,Ritanserin ,Citalopram ,Motor Activity ,Serotonergic ,Piperazines ,Mice ,Reboxetine ,Serotonin Agents ,Internal medicine ,Fluoxetine ,Fenclonine ,medicine ,Organometallic Compounds ,Animals ,Rats, Wistar ,Biological Psychiatry ,Swimming ,Pharmacology ,Aspartic Acid ,Adrenergic Uptake Inhibitors ,Chemistry ,Antidepressive Agents ,Rats ,Serotonin pathway ,Endocrinology ,Zinc Compounds ,Serotonin Antagonists ,human activities ,Selective Serotonin Reuptake Inhibitors ,medicine.drug - Abstract
Recent preclinical data indicated the antidepressant-like activity of zinc in different tests and models of depression. The present study investigates the involvement of the serotonergic system in zinc activity in the forced swim test (FST) in mice and rats. The combined treatment of sub-effective doses of zinc (hydroaspartate, 2.5 mg Zn/kg) and citalopram (15 mg/kg), fluoxetine (5 mg/kg) but not with reboxetine (2.5 mg/kg) significantly reduces the immobility time in the FST in mice. These treatments had no influence on the spontaneous locomotor activity. Moreover, while the antidepressant-like effect of zinc (5 mg/kg) in the FST was significantly blocked by pretreatment with inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA, 3x200 mg/kg), 5HT-2(A/C) receptor antagonist, ritanserin (4 mg/kg) or 5HT-1A receptor antagonist, WAY 1006335 (0.1 mg/kg), the zinc-induced reduction in the locomotor activity was not affected by these serotonin modulator agents. These results indicate the specific involvement of the serotonergic system in antidepressant but not the motion behavior of zinc in mice. Also, an increase in the swimming but not climbing parameter of the rat FST observed following zinc administration (2.5 and 5 mg Zn/kg) indicates the serotonin pathway participation. This present data indicates that the antidepressant-like activity of zinc observed in the FST involves interaction with the serotonergic system.
- Published
- 2008
241. Preliminary evaluation of pharmacological properties of some xanthone derivatives
- Author
-
Barbara Filipek, Edward Szneler, Henryk Marona, Marek T. Cegla, Natalia Szkaradek, Anna Rapacz, Małgorzata Dybała, and Agata Siwek
- Subjects
Male ,Stereochemistry ,medicine.medical_treatment ,Xanthones ,Clinical Biochemistry ,Pharmaceutical Science ,Adrenergic ,Pharmacology ,Antiarrhythmic agent ,Biochemistry ,Chemical synthesis ,Xanthone Derivatives ,antiarrhythmic ,Electrocardiography ,Mice ,Receptors, Adrenergic, alpha-2 ,Seizures ,Receptors, Adrenergic, alpha-1 ,Drug Discovery ,hypotensive and anticonvulsive activities ,Radioligand ,medicine ,Animals ,xanthones ,Rats, Wistar ,Molecular Biology ,Antihypertensive Agents ,Chemistry ,radioligand-binding assay ,Organic Chemistry ,Biological activity ,Adrenergic alpha-2 Receptor Antagonists ,Ligand (biochemistry) ,Rats ,Kinetics ,Anticonvulsant ,Adrenergic alpha-1 Receptor Antagonists ,Molecular Medicine ,Anticonvulsants ,Anti-Arrhythmia Agents - Abstract
A series of xanthone derivatives were synthesized and examined for electrocardiographic, antiarrhythmic, hypotensive and anticonvulsant activities as well as for alpha(1)- and beta(1)-adrenergic binding affinities. Among the investigated compounds, some of them exhibited significant antiarrhythmic and/or hypotensive activity. The data obtained via receptor binding assay are in agreement with pharmacological results and could explain antiarrhythmic and/or hypotensive activity of the newly synthesized structures.
- Published
- 2008
242. Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT1A activity, part 1
- Author
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Franciszek Herold, Andrzej Chodkowski, Łukasz Izbicki, Marek Król, Jerzy Kleps, Jadwiga Turło, Gabriel Nowak, Katarzyna Stachowicz, Małgorzata Dybała, and Agata Siwek
- Subjects
Pharmacology ,Male ,Serotonin Plasma Membrane Transport Proteins ,Pyridines ,Organic Chemistry ,pyrido[1,2-c]pyrimidines ,General Medicine ,Hypothermia ,Serotonin 5-HT1 Receptor Agonists ,Ligands ,Piperazines ,Body Temperature ,Immobilization ,Mice ,5-HT$_{1A}$/5-HT$_{2A}$A dual activity ,Pyrimidines ,antidepressants ,Drug Design ,Drug Discovery ,depression ,Receptor, Serotonin, 5-HT1A ,Animals ,Piperazine ,Selective Serotonin Reuptake Inhibitors ,Swimming - Abstract
A series of new derivatives of 4-aryl-pyrido[1,2-c]pyrimidine containing the 3-(4-piperidyl)-1H-indole residue or its 5-methoxy derivative were synthesized. They were characterized (i) in vitro by binding to 5-HT(1A) receptors and 5-HT transporter proteins in rat brain cortex membranes and (ii) in vivo in the mouse by induced hypothermia and forced swimming models for antagonist/agonist activity against the 5-HT(1A) autoreceptors and postsynaptic 5-HT(1A) receptors, respectively. Structure activity relationship evaluation indicated that the presence of the 3-(4-piperidyl)-1H-indole residue and ortho- or para-substituents with -F or -CH(3) groups in the aryl ring as well as an unsubstituted aryl in the 4-aryl-pyrido[1,2-c]pyrimidine moiety promoted low K(i) values for both receptors. In contrast, the presence of a 5-methoxy-3-(4-piperidyl)-1H-indole residue as well as -Cl or -OCH(3) substituents at the para position markedly reduced the receptor affinity.
- Published
- 2008
243. Antimicrobial activities of 4-substituted-3-(piperidin-4-yl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones
- Author
-
Urszula, Kosikowska, Agata, Siwek, and Maria, Dobosz
- Subjects
Antifungal Agents ,Anti-Infective Agents ,Bacteria ,Fungi ,Thiones ,Microbial Sensitivity Tests ,Triazoles ,Anti-Bacterial Agents - Published
- 2007
244. Synthesis and some pharmacological properties of 3-(piperidin-4-yl)-4-substituted-D2-1,2,4-triazoline-5-thione derivatives
- Author
-
Maria, Dobosz, Agata, Siwek, Anna, Chodkowska, and Ewa, Jagiełło-Wójtowicz
- Subjects
Male ,Analgesics ,Body Temperature ,5-Hydroxytryptophan ,Mice ,Thiazoles ,Anti-Anxiety Agents ,Piperidines ,Animals ,Anticonvulsants ,Indicators and Reagents ,Sleep ,Psychomotor Performance ,Central Nervous System Agents ,Pain Measurement - Abstract
Synthesis of 3-(piperidin-4-yl)-4-substituted-D-2-1,2,4-triazoline-5-thione derivatives, AS-1-AS-4 is described. Results of a preliminary pharmacological screening of two compounds AS-1 and AS-3 are presented.
- Published
- 2005
245. Chronic MTEP treatment, like antidepressants, induces adaptive changes in mGlu5 receptors in the rat brain
- Author
-
Lucyna Pomierny-Chamioło, Agata Siwek, Gabriel Nowak, and Andrzej Pilc
- Subjects
Pharmacology ,MTEP ,Pharmacotherapy ,business.industry ,Mglu5 receptors ,Medicine ,Adaptive change ,General Medicine ,Rat brain ,business ,Neuroscience - Published
- 2012
246. Involvement of the serotonergic and glutamatergic systems in the antidepressant-like activity of MTEP, in the forced swim test in mice
- Author
-
Agata Siwek, Lucyna Pomierny-Chamioto, Gabriel Nowak, and Anna Piotrowska
- Subjects
Pharmacology ,Glutamatergic ,MTEP ,business.industry ,Medicine ,General Medicine ,business ,Serotonergic ,Neuroscience ,Behavioural despair test ,Antidepressant like - Published
- 2010
247. Lack of NMDA–AMPA interaction in antidepressant-like effect of CGP 37849, an antagonist of NMDA receptor, in the forced swim test
- Author
-
Ewa Poleszak, Agata Siwek, Andrzej Pilc, Gabriel Nowak, and Małgorzata Dybała
- Subjects
N-Methylaspartate ,CGP-37849 ,AMPA receptor ,Motor Activity ,Pharmacology ,Receptors, N-Methyl-D-Aspartate ,Mice ,chemistry.chemical_compound ,Quinoxalines ,Animals ,2-Amino-5-phosphonovalerate ,alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ,Swimming ,Biological Psychiatry ,Depressive Disorder ,Chemistry ,Antagonist ,Antidepressive Agents ,Psychiatry and Mental health ,nervous system ,Neurology ,Competitive antagonist ,NMDA receptor ,NBQX ,Neurology (clinical) ,Excitatory Amino Acid Antagonists ,Behavioural despair test - Abstract
The NMDA receptor antagonist, CGP 37849-induced reduction in immobility time in the forced swim test in mice was not antagonized by pre-treatment with the AMPA receptor antagonist NBQX. This is the first demonstration of the antidepressant effect of the NMDA antagonist not being dependent on the AMPA transmission.
- Published
- 2008
248. 4-Methyl-N-(4-oxo-2-thioxoimidazolidin-3-yl)-1,2,3-thiadiazole-5-carboxamide
- Author
-
Irena Wawrzycka-Gorczyca, Maria Dobosz, and Agata Siwek
- Subjects
Chemistry ,medicine.drug_class ,Hydrogen bond ,Carboxamide ,General Chemistry ,Crystal structure ,Dihedral angle ,Condensed Matter Physics ,Medicinal chemistry ,chemistry.chemical_compound ,Group (periodic table) ,Amide ,medicine ,Diazole ,General Materials Science - Abstract
The molecule of the title compound, C7H7N5O2S2, is non-planar. The dihedral angles formed by the thiohydantoin and methylthiadiazole systems with the amide group are 85.5 (1) and 38.4 (3)°, respectively. The crystal structure is stabilized by intermolecular N—H⋯N/O hydrogen bonds and short S⋯O contacts, forming a three-dimensional network.
- Published
- 2006
249. Antidepressant-like properties of (R,S)-HBK-1 and its isomers, new xanthone derivatives, in mice
- Author
-
Magdalena Jastrzębska-Więsek, Karolina Pytka, Anna Partyka, Barbara Filipek, Natalia Szkaradek, Jacek Sapa, Anna Wesołowska, Agata Siwek, Henryk Marona, and Anna Rapacz
- Subjects
Pharmacology ,Stereochemistry ,Chemistry ,General Medicine ,Antidepressant like ,Xanthone Derivatives - Published
- 2013
250. Mechanisms of morphine-venlafaxine interaction in diabetic neuropathic pain model
- Author
-
Małgorzata Dybała, Agata Siwek, Magdalena Bujalska-Zadrożny, Helena E. Makulska-Nowak, and Krystyna Cegielska-Perun
- Subjects
Pharmacology ,Pharmacotherapy ,business.industry ,Anesthesia ,Neuropathic pain ,Morphine ,Medicine ,Pharmacy ,Venlafaxine ,General Medicine ,business ,medicine.drug - Published
- 2013
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