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Biochemical Pharmacology Apr 2024Cancer is recognized as the major cause of death worldwide and the most challenging public health issues. Tumor cells exhibit molecular adaptations and metabolic... (Review)
Review
Cancer is recognized as the major cause of death worldwide and the most challenging public health issues. Tumor cells exhibit molecular adaptations and metabolic reprograming to sustain their high proliferative rate and autophagy plays a pivotal role to supply the high demand for metabolic substrates and for recycling cellular components, which has attracted the attention of the researchers. The modulation of the autophagic process sensitizes tumor cells to chemotherapy-induced cell death and reverts drug resistance. In this regard, many in vitro and in vivo studies having shown the anticancer activity of phenothiazine (PTZ) derivatives due to their potent cytotoxicity in tumor cells. Interestingly, PTZ have been used as antiemetics in antitumor chemotherapy-induced vomiting, maybe exerting a combined antitumor effect. Among the mechanisms of cytotoxicity, the modulation of autophagy by these drugs has been highlighted. Therefore, the use of PTZ derivatives can be considered as a repurposing strategy in antitumor chemotherapy. Here, we provided an overview of the effects of antipsychotic PTZ on autophagy in tumor cells, evidencing the molecular targets and discussing the underlying mechanisms. The modulation of autophagy by PTZ in tumor cells have been consistently related to their cytotoxic action. These effects depend on the derivative, their concentration, and also the type of cancer. Most data have shown the impairment of autophagic flux by PTZ, probably due to the blockade of lysosome-autophagosome fusion, but some studies have also suggested the induction of autophagy. These data highlight the therapeutic potential of targeting autophagy by PTZ in cancer chemotherapy.
Topics: Humans; Antipsychotic Agents; Phenothiazines; Drug Repositioning; Antineoplastic Agents; Autophagy; Neoplasms; Cell Line, Tumor; Apoptosis
PubMed: 38395266
DOI: 10.1016/j.bcp.2024.116075 -
Applied Microbiology and Biotechnology Dec 2022Bacterial pathogens are fostered in and transmitted through wastewater. Hence, monitoring their impact on sanitation and hygiene is imperative. As part of the monitoring...
Bacterial pathogens are fostered in and transmitted through wastewater. Hence, monitoring their impact on sanitation and hygiene is imperative. As part of the monitoring process, culture-based methodologies are primarily used, which centre on the use of selective and differential media. Media available today are, at best, difficult to formulate and, at worst, prohibitively expensive. To address this lacuna, the study proposes a selective and differential medium for Klebsiella spp. Klebsiella blue agar (KBA) is completely selective against selected gram-positive bacteria (Bacillus spp., Staphylococcus aureus) and a few gram-negative bacteria (Acinetobacter baumanii, Serratia marcescens). On the other hand, it supports the growth of the chosen members of the Klebsiella pneumoniae species-complex with a characteristic green colouration. Methylene blue, tryptophan, and bile salt make up the selective components of KBA. Moreover, methylene blue, 0.6% NaCl, and glycerol render it differential. KBA was more selective than HiCrome™ Klebsiella Selective Agar Base (KSA) in replica plating experiments. KBA promoted only 157 CFUs against 209 CFUs in KSA when stamped with 253 CFUs grown on LB. The colonies so isolated were predominantly Klebsiella spp., on identification through colony polymerase chain reaction. Moreover, the differential nature of KBA distinguished Klebsiella aerogenes from other species. On the contrary, KSA lodged colonies indistinguishable from each other and Klebsiella spp. Due to its ease of formulation, high selectivity, differential nature, and cost-effective composition, KBA is a viable option for the routine culture of Klebsiella spp. in environmental and clinical settings. KEY POINTS: • Formulated a novel selective and differential media for Klebsiella spp., named Klebsiella Blue agar • Facile formulation methodology • Can be employed to isolate Klebsiella spp. from complex sources such as wastewater.
Topics: Klebsiella; Methylene Blue
PubMed: 36380193
DOI: 10.1007/s00253-022-12270-w -
Spectrochimica Acta. Part A, Molecular... Dec 2022Fluphenazine HCl (FLU) is an anxiolytic, while Nortriptyline HCl (NOR) is an anti-depressant. They are co-formulated together to treat depression and schizophrenia....
Simultaneous spectrophotometric determination of fluphenazine HCl and nortriptyline HCl in presence of their potential impurities perphenazine and dibenzosuberone in bulk and pharmaceutical formulation.
Fluphenazine HCl (FLU) is an anxiolytic, while Nortriptyline HCl (NOR) is an anti-depressant. They are co-formulated together to treat depression and schizophrenia. Perphenazine (PER) and dibenzosuberone (DBZ) are the pharmacopeial impurities of FLU and NOR, respectively. Four spectrophotometric and multivariate chemometric methods were developed to determine the two drugs together or in presence of their two impurities in their bulk and pharmaceutical formulation. Method (A) is the triple divisor-ratio derivative (TDR) method, where the zero order spectrum of each component was divided by a mixture of the other 3 components, then the peak amplitudes of the first derivative spectra of FLU, NOR and DBZ were measured at 265, 245.4 and 283.2 nm, respectively. Method (B) is the double divisor-ratio difference-dual wavelength (DD-RD-DW) method, in which each component spectrum mixture was divided by a binary mixture of 2 of the interfering components. In the resulting ratio spectra, the amplitude difference is calculated between 2 wavelengths at which the third interfering component has zero difference. Methods (C and D) are the principle component analysis (PCA) and partial least squares (PLS) models. Methods (A and B) failed to quantify PER (FLU impurity), while (C and D) succeeded to quantify all components. The four methods have been applied for the prediction of the FLU and NOR in their pharmaceutical formulation with good accuracy and precision. The proposed methods have been validated according to the ICH guidelines and the results were within the acceptable limits.
Topics: Dibenzocycloheptenes; Drug Compounding; Fluphenazine; Nortriptyline; Perphenazine; Spectrophotometry
PubMed: 35933777
DOI: 10.1016/j.saa.2022.121695 -
Biosensors Jan 2024A new fluorescent sensor for the detection of CN was developed based on the conjugation of phenothiazine fluorophore and benzofuran unit. By the nucleophilic attacking...
A new fluorescent sensor for the detection of CN was developed based on the conjugation of phenothiazine fluorophore and benzofuran unit. By the nucleophilic attacking of CN to the fluoroacetylamino group in the sensor, the additional reaction of CN and carbonyl group induced the ICT (intramolecular charge transfer) effect in the molecule and caused the fluorescence quenching sensor. The titration experiments show that the sensor has good sensitivity, selectivity and quick response for CN. In addition, the fluorescent detection of CN in the living cell and zebrafish experiments demonstrated the value of the sensor in tracing the CN in biological systems.
Topics: Animals; Cyanides; Zebrafish; Fluorescent Dyes; Phenothiazines
PubMed: 38248428
DOI: 10.3390/bios14010051 -
Journal of Pharmaceutical Sciences Aug 2021Dioxopromethazine (DPZ) is a popular phenothiazine antihistamine that is widely used as a racemic drug in clinical to cure respiratory illness. In our work, a reliable,...
Dioxopromethazine (DPZ) is a popular phenothiazine antihistamine that is widely used as a racemic drug in clinical to cure respiratory illness. In our work, a reliable, specific, and rapid enantioselective HPLC-MS/MS method has been established and fully validated for the quantification of R- and S-DPZ in rat plasma. After plasma alkalization (with 1 M NaCO), DPZ enantiomers and diphenhydramine (IS) were extracted using ethyl acetate. Completely separation of R- and S-DPZ (Rs = 2.8) within 12 min was implemented on Chiralpak AGP column (100 × 4.0 mm i.d., 5 μm) employing ammonium acetate (10 mM; pH 4.5) - methanol (90:10, v/v) as mobile phase. Themultiple reaction monitoring (MRM) mode was used for the detection of DPZ enantiomers and IS. The transitions of m/z 317.2 → 86.1 and 256.2 → 167.1 werechosen for monitoring DPZ enantiomers and IS, respectively. Good linearity (r > 0.995) was achieved for each DPZ enantiomer over the linear ranges of 1.00 - 80.00 ng/mL, with the lower limit of quantitation (LLOQ) of 1.00 ng/mL. The intra-day and inter-day precisions (RSDs,%) were below 12.3%, and accuracies (REs,%) were in the scope of-10.5% to 6.6%, which were within the admissible criteria. The validated bioanalytical approach was applied to the stereoselective pharmacokinetic (PK) research of DPZ in rat plasma for the first time. It was found that significant differences (p < 0.05) exist between the main PK parameters of R- and S-DPZ, indicating the pharmacokinetic behaviors of DPZ enantiomers in rats were stereoselective. The chiral inversion of the enantiomers did not occur during the assay.
Topics: Animals; Chromatography, High Pressure Liquid; Plasma; Promethazine; Rats; Reproducibility of Results; Stereoisomerism; Tandem Mass Spectrometry
PubMed: 33940025
DOI: 10.1016/j.xphs.2021.04.015 -
Analytical Biochemistry Jun 2023Hypochlorite (ClO) plays a key role in life systems and it is necessary to develop an effective detection method. In view of the significant advantages of the...
Hypochlorite (ClO) plays a key role in life systems and it is necessary to develop an effective detection method. In view of the significant advantages of the fluorescent probe, we have synthesized a naked-eye recognition fluorescent probe NNCF for the detection of ClO based on phenothiazine and naphthalimide. The probe NNCF is sensitive (LOD = 9.5 nM) and fast for ClO (within 30 s), and its Stokes shift is as large as 161 nm. In addition, the probe NNCF has been successfully used for imaging detection of exogenous ClO in MCF-7 cells with low toxicity.
Topics: Humans; Fluorescent Dyes; Hypochlorous Acid; Eye Color; Phenothiazines
PubMed: 37001597
DOI: 10.1016/j.ab.2023.115131 -
Molecules (Basel, Switzerland) Aug 2020Acetylcholinesterase (AChE) and beta-secretase (BACE-1) are two attractive targets in the discovery of novel substances that could control multiple aspects of...
Acetylcholinesterase (AChE) and beta-secretase (BACE-1) are two attractive targets in the discovery of novel substances that could control multiple aspects of Alzheimer's disease (AD). Chalcones are the flavonoid derivatives with diverse bioactivities, including AChE and BACE-1 inhibition. In this study, a series of -substituted-4-phenothiazine-chalcones was synthesized and tested for AChE and BACE-1 inhibitory activities. In silico models, including two-dimensional quantitative structure-activity relationship (2D-QSAR) for AChE and BACE-1 inhibitors, and molecular docking investigation, were developed to elucidate the experimental process. The results indicated that 13 chalcone derivatives were synthesized with relatively high yields (39-81%). The bioactivities of these substances were examined with pIC 3.73-5.96 (AChE) and 5.20-6.81 (BACE-1). Eleven of synthesized chalcones had completely new structures. Two substances AC4 and AC12 exhibited the highest biological activities on both AChE and BACE-1. These substances could be employed for further researches. In addition to this, the present study results suggested that, by using a combination of two types of predictive models, 2D-QSAR and molecular docking, it was possible to estimate the biological activities of the prepared compounds with relatively high accuracy.
Topics: Chalcones; Cholinesterase Inhibitors; Molecular Docking Simulation; Phenothiazines; Quantitative Structure-Activity Relationship
PubMed: 32867308
DOI: 10.3390/molecules25173916 -
Journal of Biomolecular Structure &... Sep 2022Superoxide dismutases (SODs) are regarded as important antioxidants for protecting cells against damage arising from oxidative stress. Much research is focused on...
Superoxide dismutases (SODs) are regarded as important antioxidants for protecting cells against damage arising from oxidative stress. Much research is focused on finding new chemicals with an ability to boost human SOD activity. In the research described herein a structure-based approach was used to identify new human Cu-Zn superoxide dismutase (SOD1) modulators based on previously reported plasmodium falciparum iron SOD inhibitors using induced fit docking and molecular dynamic (MD) protocols. The compound with the highest docking binding energy was selected for further structure simplification followed by structural similarity and MD in order to find a new activator/inhibitor scaffold of the SOD1 enzyme. According to the docking survey of the mentioned series, 1,4-bis(3-(1,4,8-trichloro-10Hphenothiazin-10-yl) propyl) piperazine (DS88) was the top scoring compound interacting with the SOD1 active site channel. Following structure simplification and similarity search, the most promising scaffold which is closely related to the phenothiazine antipsychotic class, was identified. Compared with the normal blood SOD1 activity, the percent of O production increased with trifluoperazine, while it decreased with the chlorpromazine. The molecular dynamic investigation shows that trifluoperazine exerts its SOD1 activating effect by stabilizing electrostatic loop while chlorpromazine employs SOD1 inhibition activity through repositioning of the electrostatic loop and increasing its distance from the catalytic metal site which diminished substrate specificity and catalytic activity of the SOD1 enzyme. The results identified the preferred region, orientation, and types of interaction for each activator or inhibitor compound.
Topics: Catalytic Domain; Chlorpromazine; Humans; Superoxide Dismutase; Superoxide Dismutase-1; Trifluoperazine
PubMed: 33663349
DOI: 10.1080/07391102.2021.1893819 -
Carbohydrate Research Mar 2021With the development of dye and printing, production wastewater has become one of the most primary pollution sources of water and soil pollution. Most of the dyes are...
With the development of dye and printing, production wastewater has become one of the most primary pollution sources of water and soil pollution. Most of the dyes are toxic substances, which have the "three-way" effect of carcinogenic, teratogenic and mutagenic. Therefore, it is a very difficult but significant issue to deal with the dye in the wastewater. Here, we report a study on low-cost, high-capacity hydrogels that remove water-soluble dyes. The hydrogel is prepared by crosslinking the β-cyclodextrin and functional monomer: acrylamido and 2-acrylamide-2-methylpropane sulfonic acid by aqueous solution polymerization, meanwhile, alkaline hydrolysis is also an important step for adsorption performance. After alkaline hydrolysis, the amide and sulfonic groups in the hydrogel were converted into carboxylate and sulfonate, which was beneficial to the adsorption of cationic dyes. This polymer could remove 96.58% methylene blue (400 mg/L) and only requires 0.02 wt%. Its maximum adsorption capacity for methylene blue could reach 2638.22 mg/g under equilibrium condition. It is the most powerful adsorbent used to treat dye wastewater, according to the report. It also provides some references for hydrogel treatment of dye wastewater.
Topics: Adsorption; Hydrogels; Methylene Blue; Molecular Structure; Particle Size; Surface Properties; Water Pollutants, Chemical; beta-Cyclodextrins
PubMed: 33662813
DOI: 10.1016/j.carres.2021.108276 -
Environmental Research Nov 2022Zirconium oxide nanoparticles (ZrONPs) were prepared using the leaf extract of Muntingia calabura as a reductant. The absorption peak at 232 nm confirmed the signature...
Zirconium oxide nanoparticles (ZrONPs) were prepared using the leaf extract of Muntingia calabura as a reductant. The absorption peak at 232 nm confirmed the signature peak for ZrONPs with band energy at 5.07 eV. The ZrONPs were tetragonal and highly crystalline, possessing a mean diameter of 14.83 nm as confirmed by XRD studies. The lattice constants (a = 0.362 nm and c = 0.511 nm) were consistent with the literature. Spherical nanoaggregates (29.25 nm) were seen in FESEM image and the specific signals for Zr and O were noticed in EDS image. The tetragonal phase of the ZrONPs were further confirmed from the XPS and Raman studies. PL spectrum had a sharp emission at 493 nm. The FTIR spectrum revealed the presence of various functional groups. ZrONPs were thermally stable with 5.76% total weight loss - as revealed from TGA profile. The photocatalytic breakdown of methylene blue (MB) dye under the influence of solar irradiation was performed using ZrONPs which exhibited 89.11% degradation within 5 h. Hence, the synthesized ZrONPs can be used as an alternate potential photocatalyst for the degradation of various dyes present in waste streams.
Topics: Catalysis; Coloring Agents; Methylene Blue; Nanoparticles; Zirconium
PubMed: 35793722
DOI: 10.1016/j.envres.2022.113785