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1.
J Mater Chem B ; 11(44): 10692-10705, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37917006

RESUMO

A nanocomposite of (2-aminoethyl)piperazine ligand substituted with zinc(II) tetra carboxylic acid phthalocyanine (ZnTEPZCAPC) and MWCNTs was constructed and employed to develop an electrochemical sensor with outstanding sensitivity and a low detection limit. The macrocyclic complex ZnTEPZCAPC was first synthesized and then employed for the electrochemical determination of the antipsychotic drug promazine (PMZ). The as-prepared ZnTEPZCAPC and MWCNT nanocomposite was characterized using different techniques, such as Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), UV-visible spectroscopy (UV-Vis), field emission scanning electron microscopy (FE-SEM), and thermogravimetric analysis (TGA). Further, the prepared ZnTEPZCAPC@MWCNT nanocomposites were modified on a glassy carbon electrode (GCE) surface, and the electrochemical activity was investigated using cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry (CA) tests in pH 7.0 phosphate buffer solution (PBS) in the potential window of 0.0-1 V. The ZnTEPZCAPC@MWCNTs displayed a superior electrochemical performance because of their high electrochemical active surface area (0.453 cm2), good conductivity, and a synergetic effect. The developed electrochemical sensor exhibited a broad linear range of 0.05-635 µM and the lowest detection limit of 0.0125 nM, as well as excellent sensitivity, repeatability, and reproducibility. Finally, the fabricated sensor was successively used for the real-time detection of PMZ in environmental and biological samples and displayed feasible recoveries.


Assuntos
Antipsicóticos , Promazina , Espectroscopia de Infravermelho com Transformada de Fourier , Reprodutibilidade dos Testes , Zinco , Piperazinas
2.
Environ Sci Pollut Res Int ; 30(34): 82387-82405, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37326738

RESUMO

This research aims to remove two phenothiazines, promazine (PRO) and promethazine (PMT), from their individual and binary mixtures using olive tree pruning biochar (BC-OTPR). The impact of individual and combinatory effects of operational variables was evaluated for the first time using central composite design (CCD). Simultaneous removal of both drugs was maximized utilizing the composite desirability function. At low concentrations, the uptake of PRO and PMT from their individual solutions was achieved with high efficiency of 98.64%, 47.20 mg/g and 95.87%, 38.16 mg/g, respectively. No major differences in the removal capacity were observed for the binary mixtures. Characterization of BC-OTPR confirmed successful adsorption and showed that the OTPR surface was predominantly mesoporous. Equilibrium investigations revealed that the Langmuir isotherm model best describes the sorption of PRO/PMT from their individual solutions with maximum adsorption capacities of 640.7 and 346.95 mg/g, respectively. The sorption of PRO/PMT conforms to the pseudo-second-order kinetic model. Regeneration of the adsorbent surface was successfully done with desorption efficiencies of 94.06% and 98.54% for PRO and PMT, respectively, for six cycles.


Assuntos
Olea , Poluentes Químicos da Água , Águas Residuárias , Prometazina , Promazina , Cinética , Adsorção , Carvão Vegetal , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio
3.
J Appl Toxicol ; 43(4): 474-489, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36165981

RESUMO

In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the treatment of schizophrenia, which is related to altered neurotransmission and dysregulation of neuronal autophagy. Thus, phenothiazine derivatives can impact autophagy. We identified 35 papers, where the use of the phenothiazines in the in vitro autophagy assays on normal and cancer cell lines, Caenorhabditis elegans, and zebrafish were discussed. Chlorpromazine, fluphenazine, mepazine, methotrimeprazine, perphenazine, prochlorperazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate autophagy. Stimulation of autophagy by phenothiazines may be either mammalian target of rapamycin (mTOR)-dependent or mTOR-independent. The final effect depends on the used concentration as well as the cell line. A further investigation of the mechanisms of autophagy regulation by phenothiazine derivatives is required to understand the biological actions and to increase the therapeutic potential of this class of drugs.


Assuntos
Antipsicóticos , Animais , Antipsicóticos/toxicidade , Peixe-Zebra , Promazina , Fenotiazinas/farmacologia , Clorpromazina/farmacologia , Mamíferos
4.
Psychiatr Danub ; 34(2): 245-252, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35772134

RESUMO

BACKGROUND: To assess potential benefits of quetiapine for persistent sleep disturbances in patients with posttraumatic stress disorder (PTSD) on stable combined SSRI and benzodiazepine therapy, who previously failed to respond to various benzodiazepine and non-benzodiazepine hypnotic adjuvant treatment as well as to first-generation antipsychotic add-on treatment. SUBJECTS AND METHODS: Fifty-two male PTSD outpatients on stable combination treatment with SSRI and benzodiazepines, with persistent sleep disturbances not responding to prescription of zolpidem, flurazepam, nitrazepam, promazine, and levopromazine, were assessed for sleep disturbances improvements after prescription of quetiapine in the evening. Each patient met both ICD-10 and DSM-IV criteria for PTSD. Psychiatric comorbidity and premorbidity were excluded using the Mini-International Neuropsychiatric Interview (MINI). Improvement on the CAPS recurrent distressing dream item, reduction in the amount of time needed to fall asleep, prolongation of sleep duration, and reduction in average number of arousals per night in the last 7 days before the assessment period were used as efficacy measures. RESULTS: All sleep-related parameters improved significantly at the end of a five-week follow-up: sleep duration increased by one hour (p<0.001), sleep latency decreased by 52.5 minutes (p<0.001), median number of arousals per night decreased from two to one (p<0.001), CAPS recurrent distressing dream item median decreased from five to four (p<0.001), and the number of patients dissatisfied with their sleep quality and quantity decreased from 45 to two (p<0.001). CONCLUSION: Quetiapine prescribed in the evening may be successful therapy for persistent sleep disturbances in patients with PTSD and generally good response to an SSRI and benzodiazepine combination, who previously failed to respond to some of the usual hypnotic medication or addition of first-generation antipsychotics: zolpidem, flurazepam, nitrazepam, promazine, and levopromazine.


Assuntos
Antipsicóticos , Transtornos do Sono-Vigília , Transtornos de Estresse Pós-Traumáticos , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Flurazepam/farmacologia , Flurazepam/uso terapêutico , Humanos , Hipnóticos e Sedativos/uso terapêutico , Masculino , Metotrimeprazina/farmacologia , Metotrimeprazina/uso terapêutico , Nitrazepam/farmacologia , Nitrazepam/uso terapêutico , Promazina/farmacologia , Promazina/uso terapêutico , Fumarato de Quetiapina/farmacologia , Fumarato de Quetiapina/uso terapêutico , Sono/fisiologia , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/etiologia , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia , Zolpidem/farmacologia , Zolpidem/uso terapêutico
6.
J Anal Toxicol ; 46(7): 803-806, 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518883

RESUMO

Promazine is one of the oldest phenothiazine derivatives that have been proposed for the treatment of various psychiatric disorders. The drug is available as tablets, as syrups and in injectable forms. Despite its prescription to millions of subjects, its detection in human hair has seldom been reported. The aim of the present work is to develop a specific method to identify promazine in human hair by liquid chromatography-tandem mass spectrometry and to apply it to a patient who was self-medicating. The method involves overnight incubation of 20 mg of cut hair in 1 mL of pH 9.5 borate buffer in the presence of amitriptyline-d3 at 40°C. The chromatographic separation was performed using a reverse phase column HSS C18 with a gradient elution for 15 min. Linearity was verified from 0.5 to 500 pg/mg (r2 = 0.9996), after spiking blank hair with the corresponding amounts of promazine. The limit of detection was estimated at 0.1 pg/mg. The precision was lower than 20%. Promazine was detected in the hair of a psychotic subject at 228-270 pg/mg in a 3 × 1 cm segment. Given this was a patient who was self-medicating, her physician requested an immediate drug discontinuation. In a fresh hair specimen collected 3 months later, the proximal segment (0-1 cm) tested positive at 0.9 pg/mg, clearly indicating that the time to obtain a negative result after promazine discontinuation is about 3-4 months.


Assuntos
Promazina , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Feminino , Cabelo/química , Humanos , Promazina/análise , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem/métodos
7.
Biochem Biophys Res Commun ; 534: 107-113, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33316543

RESUMO

Measurement of autophagic flux in vivo is critical to understand how autophagy can be used to combat disease. Neurodegenerative diseases have a special relationship with autophagy, which makes measurement of autophagy in the brain a significant research priority. Currently, measurement of autophagic flux is possible through use of transgenic constructs, or application of a lysosomal inhibitor such as chloroquine. Unfortunately, chloroquine is not useful for measuring autophagic flux in the brain and the use of transgenic animals necessitates cross-breeding of transgenic strains and maintenance of lines, which is costly. To find a drug that could block lysosomal function in the brain for the measurement of autophagic flux, we selected compounds from the literature that appeared to have similar properties to chloroquine and tested their ability to inhibit autophagic flux in cell culture and in mice. These chemicals included chloroquine, quinacrine, mefloquine, promazine and trifluoperazine. As expected, chloroquine blocked lysosomal degradation of the autophagic protein LC3B-II in cell culture. Quinacrine also inhibited autophagic flux in cell culture. Other compounds tested were not effective. When injected into mice, chloroquine caused accumulation of LC3B-II in heart tissue, and quinacrine was effective at blocking LC3B-II degradation in male, but not female skeletal muscle. None of the compounds tested were useful for measuring autophagic flux in the brain. During this study we also noted that the vehicle DMSO powerfully up-regulated LC3B-II abundance in tissues. This study shows that chloroquine and quinacrine can both be used to measure autophagic flux in cells, and in some peripheral tissues. However, measurement of flux in the brain using lysosomal inhibitors remains an unresolved research challenge.


Assuntos
Autofagia/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cloroquina/farmacologia , Lisossomos/efeitos dos fármacos , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Células HeLa , Humanos , Lisossomos/metabolismo , Macrolídeos/farmacologia , Masculino , Mefloquina/farmacologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/metabolismo , Promazina/farmacologia , Quinacrina/farmacologia , Trifluoperazina/farmacologia
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 119012, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33039847

RESUMO

Detection and qualification process related to impurities assume importance in pharmacological drug development programmes and the present article gives the structural and spectral characterisation of phenothiazine derivatives, promazine (PME) and trifluoperazine (TPE) and their self-assembly with graphene/fullerene/carbon ring (CG/CF/CR) systems theoretically. The investigation of adsorption behaviour of these compounds can provide valuable information about its reactivity, electronic and structural properties. Three-dimensional electrostatic potential diagrams were mapped. The frontier orbital energies and energy band gaps of the molecules were computed. Delocalization of charge density between the bonding or lone pair and antibonding orbitals is calculated by NBO analysis. Docking was executed to investigate binding areas of chemical compounds. Bioactivity scores show that the pharmacokinetic and pharmacological properties of the ligands are appropriate leading to be considered potential drug agents. The obtained theoretical wavenumber results of the present study were fully compatible with the experimental results.


Assuntos
Fulerenos , Grafite , Adsorção , Promazina , Psicotrópicos , Teoria Quântica , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Trifluoperazina
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 227: 117563, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31689607

RESUMO

Phenothiazines are very effective antipsychotic drugs, which also have anticancer and antimicrobial activities. Despite being used in human treatment, the molecular mechanism of the biological actions of these molecules is not yet understood in detail. The role of the interactions between phenothiazines and proteins or lipid membranes has been much discussed. Herein, fourier-transform infrared (FTIR) spectroscopic studies were used to investigate the effect of three phenothiazines: fluphenazine (FPh); chlorpromazine (ChP); and propionylpromazine (PP) on the structures of a positively charged poly-l-lysine (PLL) peptide, a negatively charged dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol (DPPC/DPPG) membrane, and on the mutual interactions between electrostatically associated PLL molecules and DPPC/DPPG membranes. Phenothiazine-induced alterations in the secondary structure of PLL, the conformational state (trans/gauche) of the hydrocarbon lipid chains, and the hydration of the DPPC/DPPG membrane interface were studied on the basis of amide I' vibrations, antisymmetric and symmetric stretching vibrations of the CH2 groups of the lipid hydrocarbon chains (νsCH2), and stretching vibrations of the lipid C=O groups (νC = O), respectively. It was shown that in the presence of negatively charged DPPC/DPPG membranes, the phenothiazines were able to modify the secondary structure of charged PLL molecules. Additionally, the effect of PLL on the structure of DPPC/DPPG membranes was also altered by the presence of the phenothiazine molecules.


Assuntos
1,2-Dipalmitoilfosfatidilcolina/metabolismo , Antipsicóticos/farmacologia , Clorpromazina/farmacologia , Flufenazina/farmacologia , Fosfatidilgliceróis/metabolismo , Promazina/análogos & derivados , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Humanos , Polilisina/metabolismo , Promazina/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
11.
Addict Behav ; 60: 53-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27088514

RESUMO

A 24-year old woman with multisubstance use since the age of 13, including opioids and cocaine, and long-standing HIV/HCV seropositivity status, presented with psychosis, agitation, and insomnia at the emergency department of a university hospital. She had been abusive and physically aggressive frequently without specific reasons and was involved in criminal legal cases. She was hospitalized twice. During her first hospital stay she experienced a brief episode of detachment from her environment, similar to episodes reportedly suffered at home. Psychosis had developed following heavy polysubstance abuse. Her mother provided sachets containing benzylglycinamide, a substance with no known psychotropic effects, which were also present in the patient's urine. She was occasionally positive for cannabinoids. She used to buy various novel psychoactive substances (NPSs) from the internet and used experimentally various substances freely made available to her by drug suppliers/dealers. She was unable to explain clearly why she was taking any of the identified NPS. She stated she was taking benzylglycinamide to calm her when smoking synthetic cannabinoids. While it appears that benzylglycinamide is not likely to constitute a novel drug of abuse, her polysubstance use exemplifies trends in NPS use patterns among the youths in the Western world and should alert mental health workers as to the possible dangers of such behavior and its reflection on social behavior and psychopathology.


Assuntos
Glicina/análogos & derivados , Infecções por HIV/complicações , Psicoses Induzidas por Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Ansiolíticos/uso terapêutico , Antirretrovirais/uso terapêutico , Antipsicóticos/uso terapêutico , Feminino , Glicina/sangue , Glicina/urina , Infecções por HIV/tratamento farmacológico , Humanos , Drogas Ilícitas/sangue , Drogas Ilícitas/urina , Itália , Lorazepam/uso terapêutico , Palmitato de Paliperidona/uso terapêutico , Promazina/uso terapêutico , Psicoses Induzidas por Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/urina , Adulto Jovem
12.
Eur J Pharm Sci ; 83: 36-44, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26690045

RESUMO

The feasibility of titanium dioxide (TiO2) photocatalysis, electrochemically assisted Fenton reaction (EC-Fenton) and direct electrochemical oxidation (EC) for simulation of phase I metabolism of drugs was studied by comparing the reaction products of buspirone, promazine, testosterone and 7-ethoxycoumarin with phase I metabolites of the same compounds produced in vitro by human liver microsomes (HLM). Reaction products were analysed by UHPLC-MS. TiO2 photocatalysis simulated the in vitro phase I metabolism in HLM more comprehensively than did EC-Fenton or EC. Even though TiO2 photocatalysis, EC-Fenton and EC do not allow comprehensive prediction of phase I metabolism, all three methods produce several important metabolites without the need for demanding purification steps to remove the biological matrix. Importantly, TiO2 photocatalysis produces aliphatic and aromatic hydroxylation products where direct EC fails. Furthermore, TiO2 photocatalysis is an extremely rapid, simple and inexpensive way to generate oxidation products in a clean matrix and the reaction can be simply initiated and quenched by switching the UV lamp on/off.


Assuntos
Buspirona/química , Cumarínicos/química , Promazina/química , Testosterona/química , Titânio/química , Buspirona/metabolismo , Catálise , Cumarínicos/metabolismo , Remoção de Radical Alquila , Eletroquímica , Humanos , Hidrogenação , Hidroxilação , Ferro/química , Microssomos Hepáticos/metabolismo , Oxirredução , Promazina/metabolismo , Testosterona/metabolismo , Titânio/efeitos da radiação , Raios Ultravioleta
13.
Anal Chem ; 87(4): 2242-8, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25615803

RESUMO

The effects of medicine on the biomolecular interaction have been given increasing attention in biochemistry and affinity-based analytics since the environment in vivo is complex especially for the patients. Herein, myoglobin, a biomarker of acute myocardial infarction, was used as a model, and the medicine effects on the interactions of myoglobin/aptamer and myoglobin/antibody were systematically investigated using atomic force microscopy (AFM) for the first time. The results showed that the average binding force and the binding probability of myoglobin/aptamer almost remained unchanged after myoglobin-modified gold substrate was incubated with promazine, amoxicillin, aspirin, and sodium penicillin, respectively. These parameters were changed for myoglobin/antibody after the myoglobin-modified gold substrate was treated with these medicines. For promazine and amoxicillin, they resulted in the change of binding force distribution of myoglobin/antibody (i.e., from unimodal distribution to bimodal distribution) and the increase of binding probability; for aspirin, it only resulted in the change of the binding force distribution, and for sodium penicillin, it resulted in the increase of the average binding force and the binding probability. These results may be attributed to the different interaction modes and binding sites between myoglobin/aptamer and myoglobin/antibody, the different structures between aptamer and antibody, and the effects of medicines on the conformations of myoglobin. These findings could enrich our understanding of medicine effects on the interactions of aptamer and antibody to their target proteins. Moreover, this work will lay a good foundation for better research and extensive applications of biomolecular interaction, especially in the design of biosensors in complex systems.


Assuntos
Anticorpos/química , Aptâmeros de Nucleotídeos/química , Microscopia de Força Atômica , Mioglobina/química , Amoxicilina/química , Amoxicilina/farmacologia , Anticorpos/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Aspirina/química , Aspirina/farmacologia , Sítios de Ligação/efeitos dos fármacos , Biomarcadores/química , Biomarcadores/metabolismo , Ouro/química , Mioglobina/metabolismo , Penicilina G/química , Penicilina G/farmacologia , Promazina/química , Promazina/farmacologia , Ligação Proteica/efeitos dos fármacos
15.
Int J Pharm ; 475(1-2): 270-81, 2014 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-25148730

RESUMO

Phenothiazine drugs - chlorpromazine (CPZ), promazine (PZ) and promethazine (PMZ) - were exposed to 266 nm (fourth harmonic of the Nd:YAG pulsed laser radiation) in order to be modified at molecular level and to produce an enhancement of their antibacterial activity. The irradiated samples were analysed by several methods: pH and surface tension measurements, UV-vis-NIR absorption spectroscopy, laser induced fluorescence and thin layer chromatography. The purpose of these investigations was to study and describe the modified properties of the medicines to further investigate their specific interactions with materials such as cotton, polyester and Parafilm M as a model smooth surface. The textile materials may be impregnated with phenothiazines drug solutions exposed to laser radiation in order to be used in treatments applied on the surface of the organism. Some of the phenothiazines solutions exposed prolonged time intervals to laser radiation have much better activity against several bacteria. Therefore, in the paper, it is reported the wetting behaviour of CPZ, PZ and PMZ solutions, irradiated for time intervals between 1 and 240 min, on the surfaces of the three textures in order to draw a conclusion about their wettability as a function of time.


Assuntos
Fenotiazinas/química , Soluções/química , Antibacterianos/química , Clorpromazina/química , Cromatografia em Camada Fina/métodos , Fibra de Algodão , Concentração de Íons de Hidrogênio , Lasers , Parafina/química , Poliésteres/química , Promazina/química , Prometazina/química , Tensão Superficial , Molhabilidade
16.
Talanta ; 125: 1-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24840407

RESUMO

The development of a field-amplified sample stacking technique is presented. Sensitivity enhancement in this technique was obtained by repetitive injections of a sample followed by steps of sample matrix removal through the application of counter-pressure. Under optimized conditions the background electrolyte (BGE) was composed of 80 mM H3PO4 while the sample matrix contained 0.5mM H3PO4 and 30% (v/v) methanol. The elaborated method enabled a 4-fold effective injection of the sample (53 s, 0.5 psi). Each injection was followed by a focusing step during which the application of a voltage (2 kV) and counter-pressure (-1 psi) was performed for 0.65 min. The method was developed for the determination of six psychiatric drugs (opipramol, hydroxyzine, promazine, amitriptyline, fluoxetine, and thioridazine). The elaborated method was applied for analysis of human urine samples after a simple liquid-liquid extraction procedure. The detection limits obtained were in the range of 2.23-6.21 ng/mL.


Assuntos
Urinálise/métodos , Amitriptilina/urina , Antidepressivos Tricíclicos/urina , Calibragem , Cátions , Eletrólitos , Eletroforese , Eletroforese Capilar , Fluoxetina/urina , Humanos , Concentração de Íons de Hidrogênio , Hidroxizina/urina , Limite de Detecção , Opipramol/urina , Ácidos Fosfóricos/química , Pressão , Promazina/urina , Solventes/química , Temperatura , Tioridazina/urina
17.
Structure ; 22(2): 291-303, 2014 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-24373770

RESUMO

Conformational transitions of the cellular form of the prion protein, PrP(C), into an infectious isoform, PrP(Sc), are considered to be central events in the progression of fatal neurodegenerative diseases known as transmissible spongiform encephalopathies. Tricyclic phenothiazine compounds exhibit antiprion activity; however, the underlying molecular mechanism of PrP(Sc) inhibition remains elusive. We report the molecular structures of two phenothiazine compounds, promazine and chlorpromazine bound to a binding pocket formed at the intersection of the structured and the unstructured domains of the mouse prion protein. Promazine binding induces structural rearrangement of the unstructured region proximal to ß1, through the formation of a "hydrophobic anchor." We demonstrate that these molecules, promazine in particular, allosterically stabilize the misfolding initiator-motifs such as the C terminus of α2, the α2-α3 loop, as well as the polymorphic ß2-α2 loop. Hence, the stabilization effects of the phenothiazine derivatives on initiator-motifs induce a PrP(C) isoform that potentially resists oligomerization.


Assuntos
Fenotiazinas/química , Príons/química , Sítio Alostérico , Motivos de Aminoácidos , Animais , Sítios de Ligação , Clorpromazina/química , Camundongos , Simulação de Dinâmica Molecular , Promazina/química , Ligação Proteica , Desnaturação Proteica , Dobramento de Proteína , Isoformas de Proteínas/química , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
18.
Bioorg Med Chem Lett ; 23(16): 4587-90, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23856051

RESUMO

Both pharmacophore models of the human ether-à-go-go-related gene (hERG) channel blockers and phospholipidosis (PLD) inducers contain a hydrophobic moiety and a hydrophilic motif/positively charged center, so it is interesting to investigate the overlap between the ligand chemical spaces of both targets. We have assayed over 4000 non-redundant drug-like compounds for both their hERG inhibitory activity and PLD inducing potential in a quantitative high throughput screening (qHTS) format. Seventy-seven percent of PLD inducing compounds identified from the screening were also found to be hERG channel blockers, and 96.9% of the dually active compounds were positively charged. Among the 48 compounds that induced PLD without inhibiting hERG channel, 24 compounds (50.0%) carried steroidal structures. According to our results, hERG channel blockers and PLD inducers share a large chemical space. In addition, a positively charged hERG channel blocker will most likely induce PLD, while a steroid PLD inducer is less likely a hERG channel blocker.


Assuntos
Lipidoses/induzido quimicamente , Fosfolipídeos/metabolismo , Antipsicóticos/química , Antipsicóticos/farmacologia , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Humanos , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Fosfolipídeos/química , Promazina/química , Promazina/metabolismo , Promazina/farmacologia , Relação Quantitativa Estrutura-Atividade , Esteroides/química
19.
Colloids Surf B Biointerfaces ; 103: 496-501, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23261572

RESUMO

In this paper we report the effect of two cationic (imipramine hydrochloride (IMP) and promazine hydrochloride (PMZ)) and one anionic (sodium salt of ibuprofen (IBF)) drugs on the clouding behavior of a nonionic polymer hydroxypropyl methyl cellulose (HPMC). Though all the three drugs increase the cloud point (CP) of HPMC, the effect was found to be minimum in the case of IBF. Further, the effect of adding salts (NaF, NaCl, NaBr, NaNO(3), Na(2)SO(4), Na(3)PO(4), KCl, KBr, KNO(3)) in the presence of amphiphilic drugs (IMP and PMZ) on the CP of HPMC was seen. Almost linear decrease in the CP was observed with the [salt] at fixed concentrations of these drugs whereas in the absence of drugs the decrement in the CP was slight. The energetic parameters (ΔG(c)(0), ΔH(c)(0) and TΔS(c)(0)) were evaluated and it implies that the disruption of water structure becomes significantly prominent at lower concentrations of the drugs at fixed salt concentrations.


Assuntos
Metilcelulose/análogos & derivados , Preparações Farmacêuticas/química , Sais/química , Tensoativos/química , Ânions , Derivados da Hipromelose , Ibuprofeno/química , Imipramina/química , Metilcelulose/química , Micelas , Modelos Moleculares , Promazina/química , Soluções , Termodinâmica
20.
J Colloid Interface Sci ; 387(1): 194-204, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22939256

RESUMO

An evaluation of the interactions of phenothiazine tranquilizer drugs (promazine hydrochloride; PMZ and promethazine hydrochloride; PMT) with bile salts viz., sodium cholate (NaC) and sodium deoxycholate (NaDC) in aqueous medium, investigated through different physicochemical measurements is presented in this work. The mixed micellization behavior and surface properties of the phenothiazine-bile salt systems have been analyzed by conductivity and surface tension measurements. Application of different theoretical approaches to all the phenothiazine-bile salt mixtures shows a non-ideal behavior. Further, the spectroscopic techniques such as UV-visible and steady state fluorescence have been employed to study the binding of phenothiazines with bile salts. The stoichiometric ratios, binding constants (K), and free energy change (ΔG) for the phenothiazine-bile salt complexes were estimated from the Benesi-Hildebrand (B-H) double reciprocal plots obtained by using the changes in spectral intensities of phenothiazines on addition of bile salts. The results are discussed in the light of use of bile salts as promising drug delivery agents for phenothiazines and hence improve their bioavailabilty.


Assuntos
Ácido Desoxicólico/metabolismo , Promazina/metabolismo , Prometazina/metabolismo , Colato de Sódio/metabolismo , Tranquilizantes/metabolismo , Micelas , Termodinâmica
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