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Molecules (Basel, Switzerland) Apr 2021Due to the redox properties closely related to numerous physiological and pathological processes, biothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione...
Due to the redox properties closely related to numerous physiological and pathological processes, biothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), have received considerable attention in biological science. On account of the important physiological roles of these biothiols, it is of profound significance to develop sensitive and selective detection of biothiols to understand their biological profiles. In this work, we reported an efficient fluorescent probe, , for detecting biothiols in vitro and vivo, based on the phenothiazine-HPQ skeleton, with DNBS (2,4-dinitrobenzenesulfonate) as the response unit. Probe exhibited brilliant sensing performances toward thiols, including a large Stokes shift (138 nm), excellent sensitivity (for GSH, LOD = 18.3 nM), remarkable fluorescence enhancement (163-fold), low cytotoxicity, rapid response (8 min), and extraordinary selectivity. Finally, the probe illustrated herein was capable of responding and visualizing biothiols in MCF-7 cells and zebrafish.
Topics: Animals; Biosensing Techniques; Fluorescent Dyes; Glutathione; HeLa Cells; Humans; MCF-7 Cells; Optical Imaging; Phenothiazines; Quinazolinones; Sulfhydryl Compounds; Zebrafish
PubMed: 33920567
DOI: 10.3390/molecules26082337 -
British Medical Journal Sep 1971
Topics: Age Factors; Bronchopneumonia; Humans; Movement Disorders; Oxygen Inhalation Therapy; Phenothiazines
PubMed: 5569553
DOI: 10.1136/bmj.3.5776.701 -
British Medical Journal May 1975
Topics: Aged; Delayed-Action Preparations; Female; Flupenthixol; Fluphenazine; Humans; Middle Aged; Paranoid Disorders; Phenothiazines
PubMed: 1148681
DOI: 10.1136/bmj.2.5969.502-a -
British Medical Journal Apr 1967
Topics: Adult; Female; Fluphenazine; Humans; Male; Movement Disorders; Perphenazine; Pregnancy; Trifluoperazine
PubMed: 6021008
DOI: 10.1136/bmj.2.5543.55-a -
Canadian Medical Association Journal Dec 1958
Topics: Perphenazine; Phenothiazines
PubMed: 13608382
DOI: No ID Found -
Internal Medicine (Tokyo, Japan) Jun 2024This report describes a case of shock symptoms in a 72-year-old woman with epilepsy who had been in a state of polypharmacy, taking multiple antipsychotic drugs. After...
This report describes a case of shock symptoms in a 72-year-old woman with epilepsy who had been in a state of polypharmacy, taking multiple antipsychotic drugs. After receiving a normal dose of periciazine, she exhibited impaired consciousness, hypothermia, and hypotension and was admitted to hospital. Despite poor response to vasopressors, conservative treatment led to gradual improvement. Subsequent pharmacokinetic analysis showed non-toxic blood concentrations of periciazine, suggesting that even small doses of phenothiazines could result in toxic symptoms. This case highlights the importance of monitoring for adverse reactions when prescribing multiple antipsychotic drugs, particularly in older polypharmacy patients.
Topics: Humans; Aged; Female; Phenothiazines; Polypharmacy; Antipsychotic Agents; Shock; Epilepsy
PubMed: 37952960
DOI: 10.2169/internalmedicine.2012-23 -
Structure (London, England : 1993) Feb 2014Conformational 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...
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 β1, 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 β2-α2 loop. Hence, the stabilization effects of the phenothiazine derivatives on initiator-motifs induce a PrP(C) isoform that potentially resists oligomerization.
Topics: Allosteric Site; Amino Acid Motifs; Animals; Binding Sites; Chlorpromazine; Mice; Molecular Dynamics Simulation; Phenothiazines; Prions; Promazine; Protein Binding; Protein Denaturation; Protein Folding; Protein Isoforms; Protein Structure, Secondary; Protein Structure, Tertiary
PubMed: 24373770
DOI: 10.1016/j.str.2013.11.009 -
Molecules (Basel, Switzerland) Mar 2022Pharmaceuticals carried into space are subjected to different gravitational conditions. Hypergravity is encountered in the first stage, during spacecraft launching. The...
Pharmaceuticals carried into space are subjected to different gravitational conditions. Hypergravity is encountered in the first stage, during spacecraft launching. The stability of medicines represents a critical element of space missions, especially long-duration ones. Therefore, stability studies should be envisaged before the implementation of drugs for future deep space travel, where the available pharmaceuticals would be limited and restocking from Earth would be impossible. Multipurpose drugs should be proposed for this reason, such as phenothiazine derivatives that can be transformed by optical methods into antimicrobial agents. Within this preliminary study, promethazine and thioridazine aqueous solutions were exposed to UV laser radiation that modified their structures and generated a mixture of photoproducts efficient against particular bacteria. Subsequently, they were subjected to 20 g in the European Space Agency's Large Diameter Centrifuge. The aim was to evaluate the impact of hypergravity on the physico-chemical and spectral properties of unirradiated and laser-irradiated medicine solutions through pH assay, UV-Vis/FTIR absorption spectroscopy, and thin-layer chromatography. The results revealed no substantial alterations in centrifuged samples when compared to uncentrifuged ones. Due to their stability after high-g episodes, laser-exposed phenothiazines could be considered for future space missions.
Topics: Thioridazine
PubMed: 35268828
DOI: 10.3390/molecules27051728 -
Acta Poloniae Pharmaceutica 2015Cancer therapy is challenging for scientists because of low effectiveness of so far existing therapies (especially in case of great invasiveness and advanced tumor...
Cancer therapy is challenging for scientists because of low effectiveness of so far existing therapies (especially in case of great invasiveness and advanced tumor stage). Such need for new drug development and search for more efficient new findings in therapeutical applications is therefore still valid. There are also conducted studies on modifying so far existing drugs and their new methods of usage in oncology practice. One of them is phenothiazine and its derivatives which are used in psychiatric treatment for years. They also exhibit antiprion, antiviral, antibacterial and antiprotozoal properties. Cytotoxic activity, influence on proliferation, ability to induce apoptosis suggest also a possibility of phenothiazine derivatives usage in cancer cells termination. The aim of our the study was to evaluate the influence of two amine derivatives of phenothiazine on cancer cells in vitro. Amelanotic melanoma C-32 cell line (ATCC) and glioma SNB-19 cells (DSMZ) were used in this study and two derivatives were analyzed. In view of examined substances tumor potential toxicity cells proliferation and viability exposed to phenothiazine derivatives were established. Cell cycle regulatory genes expression (TP53 and CDKN1A), S-phase marker--H3 gene and intracellular apoptosis pathway genes (BAX, BCL-2) were analyzed using RT-QPCR method. The influence of examined derivatives on total cell oxidative status (TOS), total antioxidative status (TAS), malondialdehyde concentration (MDA) and superoxide dismutase activity (SOD) were analyzed. As a result, examined phenothiazine derivatives cytotoxic action on C-32 and SNB-19 and also cells proliferation inhibition were determined. Cell cycle regulatory genes (TP53, CDKN1A) expression and protein products of genes involved in mitochondial apoptosis pathway (BAX, BCL-2) expression are changed by the presence of phenothiazine derivatives during culturing. There were also noted small changes in redox potential in cells exposed to two mentioned phenothiazine derivatives.
Topics: Amines; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Genes, p53; Glioma; Humans; Melanoma, Amelanotic; Phenothiazines; Proto-Oncogene Proteins c-bcl-2
PubMed: 26665397
DOI: No ID Found -
Basic & Clinical Pharmacology &... Jan 2005The antimicrobial activity of the phenothiazine derivatives thioridazine and prochlorperazine have been evaluated with 11 Enterococcus faecalis strains and 9...
The antimicrobial activity of the phenothiazine derivatives thioridazine and prochlorperazine have been evaluated with 11 Enterococcus faecalis strains and 9 Enterococcus faecium strains, originating from human infections and animal faecal flora. We found that all E. faecalis and E. faecium strains, regardless of their susceptibility to commonly used antibiotics, were inhibited by thioridazine at a concentration of 16-32 microg/ml and by prochlorperazine at a concentration of 32-64 microg/ml. Combinations of the antibiotics vancomycin or ampicillin and thioridazine and prochlorperazine at subinhibitory concentrations, could render vancomycin- or ampicillin-resistant bacteria sensitive to each of the antibiotics. Verapamil and reserpine, inhibitors of P-glycoprotein-mediated multidrug resistance, did not reduce resistance. Our results outline modification of resistance in enterococci induced by phenothiazine derivatives unrelated to P-glycoprotein-mediated multidrug resistance.
Topics: ATP-Binding Cassette Transporters; Ampicillin; Animals; Calcium Channel Blockers; Culture Media; Drug Resistance, Multiple, Bacterial; Enterococcus faecalis; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Penicillins; Phenothiazines; Reserpine; Verapamil
PubMed: 15667593
DOI: 10.1111/j.1742-7843.2005.pto960105.x