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Biomolecules Aug 2019A comparative study of melanin and ommochrome-containing samples, isolated from the black soldier fly (BSF) by enzymatic hydrolysis, alkaline and acid alcohol extraction...
A comparative study of melanin and ommochrome-containing samples, isolated from the black soldier fly (BSF) by enzymatic hydrolysis, alkaline and acid alcohol extraction or by acid hydrolysis, was carried out. Melanin was isolated both as a melanin-chitin complex and as a water-soluble melanin. Acid hydrolysis followed by delipidization yielded a more concentrated melanin sample, the electron spin resonance (ESR) signal of which was 2.6 × 10 spin/g. The ommochromes were extracted from the BSF eyes with acid methanol. The antiradical activity of BSF melanins and ommochromes was determined by the method of quenching of luminol chemiluminescence. It has been shown that delipidization of water-soluble melanin increases its antioxidant properties. A comparison of the antioxidant activity of BSF melanins and ommochromes in relation to photoinduced lipid peroxidation was carried out. The ESR characteristics of native and oxidized melanins and ommochromes were studied. It is assumed that adult flies can be a useful source of natural pigments with antioxidant properties.
Topics: Adsorption; Animals; Antioxidants; Electron Spin Resonance Spectroscopy; Hydrogen Peroxide; Light; Lipid Peroxidation; Melanins; Phenothiazines; Simuliidae
PubMed: 31450873
DOI: 10.3390/biom9090408 -
Journal of Enzyme Inhibition and... Dec 2023Carbonic anhydrases (CAs) are important regulators of pH homeostasis and participate in many physiological and pathological processes. CA activators (CAAs) are becoming...
Antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants potently activate pharmacologically relevant human carbonic anhydrase isoforms II and VII.
Carbonic anhydrases (CAs) are important regulators of pH homeostasis and participate in many physiological and pathological processes. CA activators (CAAs) are becoming increasingly important in the biomedical field since enhancing CA activity may have beneficial effects at neurological level. Here, we investigate selected antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants (TCAs) as potential activators of human CAs I, II, IV, and VII. Our findings indicate that these compounds are more effective at activating hCA II and VII compared to hCA I and IV. Overall, hCA VII was the most efficiently activated isoform, particularly by phenothiazines and TCAs. This is especially relevant since hCA VII is the most abundant isoform in the central nervous system (CNS) and is implicated in neuronal signalling and bicarbonate balance regulation. This study offers additional insights into the pharmacological profiles of clinically employed drugs and sets the ground for the development of novel optimised CAAs.
Topics: Humans; Antipsychotic Agents; Antidepressive Agents, Tricyclic; Carbonic Anhydrases; Protein Isoforms; Phenothiazines; Histamine Antagonists; Carbonic Anhydrase Inhibitors; Structure-Activity Relationship; Molecular Structure
PubMed: 36912265
DOI: 10.1080/14756366.2023.2188147 -
Molecules (Basel, Switzerland) Aug 2022The phenothiazine derivatives, tricyclic 10-3,6-diazaphenothiazine () and pentacyclic 7-(3'-dimethylaminopropyl)diquinothiazine (), have recently been shown to exhibit...
The phenothiazine derivatives, tricyclic 10-3,6-diazaphenothiazine () and pentacyclic 7-(3'-dimethylaminopropyl)diquinothiazine (), have recently been shown to exhibit promising anticancer activities in vitro. In this report, we demonstrated that and could be pro-apoptotic agents in lung carcinoma, the human lung carcinoma A549 and non-small lung carcinoma H1299, in the range of IC = 1.52-12.89 µM, with a protective potential to healthy cell lines BEAS-2B and NHDF. The compounds showed higher activity in the range of the tested concentrations and low cytotoxicity in relation to normal healthy cells than doxorubicin, used as the reference drug. The cytostatic potential of and was demonstrated with the use of MTT assay. Cell cycle analysis via flow cytometry using Annexin-V assay showed the pro-apoptotic and pro-necrotic role of the studied diazaphenothiazines in the cell cycle. and initiated a biological response in the investigated cancer models with a different mechanism and at a different rate. Based on these findings, it can be concluded that and have potential as chemotherapeutic agents.
Topics: Antineoplastic Agents; Apoptosis; Carcinoma; Cell Line; Cell Line, Tumor; Cell Proliferation; Humans; Lung; Lung Neoplasms; Phenothiazines
PubMed: 36014495
DOI: 10.3390/molecules27165255 -
Basic & Clinical Pharmacology &... Aug 2010The antimicrobial and resistance-reversal activities of seven phenothiazine derivatives were evaluated against vancomycin-sensitive Enterococcus faecalis ATCC 29212,...
The antimicrobial and resistance-reversal activities of seven phenothiazine derivatives were evaluated against vancomycin-sensitive Enterococcus faecalis ATCC 29212, vancomycin resistant E. faecalis ATCC 51299 and ten vancomycin-resistant E. faecium strains originating from human infections. Minimum inhibitory concentrations (MIC) of the compounds were determined by agar dilution method, and synergy between phenothiazines and vancomycin was investigated using Checkerboard (microbroth dilution) technique. We found that all enterococci strains, regardless of their susceptibility to vancomycin, were inhibited by phenothiazines at concentrations varying from 8 to 256 microg/ml, with thiethylperazine being the most potent inhibitory agent. Besides, all the phenothiazines showed partial synergy with vancomycin and could lessen MIC of vancomycin from 512 to 8 microg/ml at their sub-inhibitory concentrations. The highest reduction in MIC was observed with chlorpromazine (32 times); however, thiethylperazine and promethazine stood next (24 times). Although resistance modification was observed at concentrations higher than those that phenothiazines reach in vivo, the potential offered by non-antibiotics justify further animal experiments as well as clinical trials to establish their clinical relevance.
Topics: Anti-Bacterial Agents; Drug Synergism; Drug Therapy, Combination; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Phenothiazines; Vancomycin; Vancomycin Resistance
PubMed: 20353486
DOI: 10.1111/j.1742-7843.2010.00558.x -
Canadian Medical Association Journal Sep 1964Thioridazine, chlorpromazine and trifluoperazine were administered to six psychiatric patients. Each was used in four dosage levels (thioridazine and chlorpromazine:...
Thioridazine, chlorpromazine and trifluoperazine were administered to six psychiatric patients. Each was used in four dosage levels (thioridazine and chlorpromazine: 200, 400, 800 and 1200 mg. daily; trifluoperazine: 8, 16, 32, 64 mg. daily); and each increase in dosage was effected after four days of drug administration.Before the trial, twice during each drug period and before commencement of the next dose regimen, an electrocardiogram (ECG) was recorded. The findings indicated that thioridazine modifies the terminal portion (S-T segment, T and U waves) of the human ECG. A similar change occurred in three of six subjects while taking chlorpromazine and in one of six while taking trifluoperazine. Thioridazine induced changes in all six subjects studied, viz., blunting and notching of T waves with or without prolongation of QT interval. In some the notching produced a doublehump appearance in which a T wave of reduced voltage formed the proximal hump and a positive U wave of increased voltage formed the distal hump.Thioridazine-induced alterations in the ECG have been described as resembling those caused by quinidine; they also resemble changes associated with hypokalemia.
Topics: Antipsychotic Agents; Biomedical Research; Chlorpromazine; Electrocardiography; Pharmacology; Phenothiazines; Research; Schizophrenia; Thioridazine; Toxicology; Trifluoperazine
PubMed: 14176059
DOI: No ID Found -
International Journal of Molecular... Nov 2021A series of new tertiary phenothiazine derivatives containing a quinoline and a pyridine fragment was synthesized by the reaction of...
A series of new tertiary phenothiazine derivatives containing a quinoline and a pyridine fragment was synthesized by the reaction of 1-methyl-3-benzoylthio-4-butylthioquinolinium chloride with 3-aminopyridine derivatives bearing various substituents on the pyridine ring. The direction and mechanism of the cyclization reaction of intermediates with the structure of 1-methyl-4-(3-pyridyl)aminoquinolinium-3-thiolate was related to the substituents in the 2- and 4-pyridine position. The structures of the compounds were analyzed using H, C NMR (COSY, HSQC, HMBC) and X-ray analysis, respectively. Moreover, the antiproliferative activity against tumor cells (A549, T47D, SNB-19) and a normal cell line (NHDF) was tested. The antibacterial screening of all the compounds was conducted against the reference and quality control strain ATCC 29213, three clinical isolates of methicillin-resistant (MRSA). In silico computation of the intermolecular similarity was performed using principal component analysis (PCA) and hierarchical clustering analysis (HCA) on the pool of structure/property-related descriptors calculated for the novel tetracyclic diazaphenothiazine derivatives. The distance-oriented property evaluation was correlated with the experimental anticancer activities and empirical lipophilicity as well. The quantitative shape-based comparison was conducted using the CoMSA method in order to indicate the potentially valid steric, electronic and lipophilic properties. Finally, the numerical sampling of similarity-related activity landscape (SALI) provided a subtle picture of the SAR trends.
Topics: Anti-Bacterial Agents; Antineoplastic Agents; Heterocyclic Compounds; Humans; Microbial Sensitivity Tests; Neoplasms; Phenothiazines; Staphylococcus aureus; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 34884631
DOI: 10.3390/ijms222312826 -
Tijdschrift Voor Psychiatrie 2007Phenothiazines can give rise to serious and sometimes irreversible dermatological and oculotoxic side effects. These effects can take the form of photosensitivity,... (Review)
Review
Phenothiazines can give rise to serious and sometimes irreversible dermatological and oculotoxic side effects. These effects can take the form of photosensitivity, grey-purple discoloration and hyperpigmentation of the skin and hyperpigmentation of the conjunctiva, cornea, lens, retina, choroidea and macula. Involvement of the retina or macula can lead to impaired vision, blurred vision, disturbed colour perception and night blindness. We describe the mechanisms that are currently believed to underlie these side-effects. We advise annual ophthalmic monitoring of patients receiving long-term treatment with phenothiazianes.
Topics: Antipsychotic Agents; Eye Diseases; Humans; Hyperpigmentation; Phenothiazines; Skin Diseases
PubMed: 17436211
DOI: No ID Found -
Dermatology Online Journal Feb 2013A 50-year-old man presented with a scaly erythema of the face, upper chest, forearms, and dorsum of the hands. He has been treated with cyamemazine for 6 months....
A 50-year-old man presented with a scaly erythema of the face, upper chest, forearms, and dorsum of the hands. He has been treated with cyamemazine for 6 months. Photopatch tests were performed and the patient was diagnosed with photoallergic reaction to cyamemazine. The drug was discontinued and a course of oral steroids was prescribed. The patient was advised to avoid light exposure. There has been no evidence of recurrence during a six-month follow-up period. Photoallergic reactions are much less frequent than phototoxic disorders. It is well known that several drugs including neuroleptics of the phenothiazine family may produce a skin eruption on light-exposed areas by dose-dependent (phototoxic) or photoallergic mechanisms. It is believed that photopatch testing, which is the clinical investigation of choice for suspected photoallergic reactions, is significantly underused in Europe and probably world-wide.
Topics: Anti-Anxiety Agents; Dermatitis, Photoallergic; Dermatitis, Phototoxic; Humans; Male; Middle Aged; Patch Tests; Phenothiazines; Photosensitizing Agents
PubMed: 23473285
DOI: No ID Found -
BioMed Research International 2021ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the...
BACKGROUND
ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the safety of ML171 after a single intraperitoneal (IP) injection in mice.
METHODS
The toxicity of a single dose of ML171 was evaluated in 6-week-old Institute of Cancer Research (ICR) mice in a good laboratory practice (GLP) laboratory. Twenty-five mice of each sex were assigned to five groups: negative control, vehicle control, and 125, 250, and 500 mg/kg of ML171. All mice were acclimatized for one week before beginning the study. Mice received an IP injection of ML171 or vehicle. The general condition and mortality of the animals were observed. The mice were sacrificed to evaluate histopathology 14 days after the administration of ML171 or vehicle.
RESULTS
Bodyweights were not significantly different in any group. Three males and one female died due to ML171 administration in the 500 mg/kg dose group. Autopsies of the surviving mice did not reveal any significant abnormalities after the injection of 125 mg/kg of ML171. However, the anterior lobe edge of the liver was thickened and adhesions between the liver and adjacent organs were observed in mice treated with 250 or 500 mg/kg of ML171. In addition, hypertrophy of centrilobular hepatocytes and inflammatory cell infiltration were observed after injection of 250 and 500 mg/kg of ML171.
CONCLUSION
Our results indicate that the lethal IP injection dose of ML171 is 500 mg/kg for both males and females. Mortality were not observed for lower doses of ML171. The safe dose of single IP ML171 in ICR mice was 250 mg/kg or less. Further studies are needed to confirm the safety of ML171 in the human body.
Topics: Animals; Drug Evaluation, Preclinical; Female; Male; Mice; Mice, Inbred ICR; NADPH Oxidase 1; Phenothiazines; Protein Isoforms; Toxicity Tests
PubMed: 34195263
DOI: 10.1155/2021/5515478 -
Journal of Endodontics Mar 2012This study evaluated the in vivo response of apical and periapical tissues of dogs' teeth with apical periodontitis after one-session endodontic treatment with and...
INTRODUCTION
This study evaluated the in vivo response of apical and periapical tissues of dogs' teeth with apical periodontitis after one-session endodontic treatment with and without antimicrobial photodynamic therapy (aPDT).
METHODS
Sixty root canals with experimentally induced apical periodontitis were instrumented and assigned to 4 groups receiving aPDT and root canal filling (RCF) or not: group aPDT+/RCF+ (n = 20): aPDT (photosensitizer phenothiazine chloride at 10 mg/mL for 3 minutes and diode laser [λ = 660 nm, 60 mW/cm(2)] for 1 minute) and RCF in the same session; group aPDT+/RCF- (n = 10); group aPDT-/RCF+ (n = 20), and group aPDT-/RCF- (n = 10). Teeth were restored, and the animals were killed after 90 days. Sections from the maxillas and mandibles were stained with hematoxylin-eosin and Mallory trichrome and examined under light microscopy. Descriptive (ie, newly formed apical mineralized tissue, periapical inflammatory infiltrate, apical periodontal ligament thickness, and mineralized tissue resorption) and quantitative (ie, periapical lesion size and number of inflammatory cells) microscopic analysis was performed. Quantitative data were analyzed by the Kruskal-Wallis and Dunn tests (α = .05).
RESULTS
In the aPDT-treated groups, the periapical region was moderately/severely enlarged with no inflammatory cells, moderate neoangiogenesis and fibrogenesis, and the smallest periapical lesions.
CONCLUSIONS
Although apical closure by mineralized tissue deposition was not achieved, the absence of inflammatory cells, moderate neoangiogenesis, and fibrogenesis in the periapical region in the groups treated with aPDT indicate that this can be a promising adjunct therapy to cleaning and shaping procedures in teeth with apical periodontitis undergoing one-session endodontic treatment.
Topics: Alveolar Bone Loss; Animals; Anti-Infective Agents; Bicuspid; Connective Tissue; Dental Pulp Exposure; Dogs; Lasers, Semiconductor; Neovascularization, Physiologic; Periapical Periodontitis; Periapical Tissue; Periodontal Ligament; Phenothiazines; Photochemotherapy; Photosensitizing Agents; Root Canal Preparation; Root Canal Therapy; Root Resorption; Time Factors; Tooth Apex
PubMed: 22341075
DOI: 10.1016/j.joen.2011.12.023