Search Results (26)

Background: Parasitic worm infections remain among the most prevalent and neglected health issues worldwide, affecting both humans and animals. Toxocariasis, caused by Toxocara spp., is a widespread zoonosis with significant public health and economic implications. Current anthelmintic treatments show limited efficacy, particularly against tissue-migrating larvae, underscoring the urgent need for new therapeutic options. This study aimed to evaluate the anthelmintic potential of H₁ antihistamines as repurposed drug candidates against Toxocara canis. Methods: Twenty-two H₁ antihistamines were screened for larvicidal activity against infective third-stage (L3) larvae of T. canis. Larval motility and morphology were assessed, and compounds with the highest efficacy were further investigated using density functional theory (DFT) to explore their electronic properties. Molecular docking simulations were also performed to predict interactions with T. canis β-tubulin. Results: Promethazine and rupatadine exhibited significant larvicidal effects, surpassing albendazole in reducing larval motility and inducing a distinct contorted morphology not observed in control or albendazole-treated larvae. DFT analyses suggested a strong electron-acceptor capacity, indicating a potential redox-based mechanism of action. Docking studies revealed favorable binding to the colchicine site of T. canis β-tubulin. Conclusions: This is the first report of larvicidal activity of antihistamines against T. canis, supporting their potential as repurposed therapeutic agents for the treatment of zoonotic helminthiases, particularly those caused by tissue-migrating nematodes. Full article

Promethazine hydrochloride (PMH) is a first-generation antipsychotic drug created from phenothiazine derivatives that is widely employed to treat psychiatric disorders in human healthcare systems. However, an overdose or long-term intake of PMH can lead to severe health issues in humans. Hence, establishing a sensitive, accurate, and efficient detection approach to detect PMH in human samples is imperative. In this study, we designed orthorhombic copper molybdate microspheres decorated on reduced graphene oxide (Cu₃Mo₂O₉/RGO) composite via the effective one-pot hydrothermal method. The structural and morphological features of the designed hybrid were studied using various spectroscopic methods. Subsequently, the electrochemical activity of the composite-modified screen-printed carbon electrode (Cu₃Mo₂O₉/RGO/SPCE) was assessed by employing voltammetric methods for PMH sensing. Owing to the uniform composition and structural benefits, the combination of Cu₃Mo₂O₉ and RGO has not only improved electrochemical properties but also enhanced the electron transport between PMH and Cu₃Mo₂O₉/RGO. As a result, the Cu₃Mo₂O₉/RGO/SPCE exhibited a broad linear range of 0.4–420.8 µM with a low limit of detection (LoD) of 0.015 µM, highlighting excellent electrocatalytic performance to PMH. It also demonstrated good cyclic stability, reproducibility, and selectivity in the presence of chlorpromazine and biological and metal compounds. Furthermore, the Cu₃Mo₂O₉/RGO/SPCE sensor displayed satisfactory recoveries for real-time monitoring of PMH in human urine and serum samples. This study delivers a promising electrochemical sensor for the efficient analysis of antipsychotic drug molecules. Full article

Hydrogels with tunable properties are of great interest for the development of advanced drug delivery systems. In this study, novel hydrogels with an interpenetrating polymer network (IPN) structure were obtained from the pH-responsive poly(methacrylic acid) (PMAA) and the neutral poly(N,N-dimethylacrylamide) (PDMAM). The newly synthesized IPN hydrogels were shown to be pH responsive with a 1.5 to 2.5 fold increase in their equilibrium swelling ratio at a pH above 5 which makes them appropriate for targeted intestine drug delivery. Moreover, their pH responsiveness was found to be strongly influenced by the IPN’s composition. The IPN hydrogels were loaded with PMH via swelling and the drug entrapment efficiency was found to depend on their swelling characteristic varying with the IPN’s composition from 20% to 60%. The drug release profiles were investigated under conditions resembling the oral route of drug application. The PMH release profiles appeared to follow Fickian diffusion at a stomach-like pH = 1.2 and sub-diffusion mechanism at an intestine-like pH = 6.8. The results from this study reveal that IPN hydrogels of PMAA and PDMAM are promising candidates for oral delivery of promethazine hydrochloridee demonstrating pH responsiveness and controllable swelling dependent on their composition. Further investigations are planned to fully reveal their potential as smart drug delivery systems. Full article

Fluorometric method for detecting of five nitrogen-based drugs concentration based on inhibition of emission Eosin Y (EY). The selection of N-drugs comprised indapamide (INDP), clomipramine hydrochloride (CMI), promethazine hydrochloride (PMH), lisinopril (LSP), and trifluoperazine hydrochloride (TFPH). The Stern–Volmer style was plotted between relative emissions of EY vs. N-drugs concentration. The standard curves were linear over the concentration range of 5–50 µg mL⁻¹ with R² > 0.9, and the LOD for INDP, CMI, PMH, LSP, and TFPH were 2.07, 1.36, 3.02, 3.52, and 2.09 µmol·L⁻¹, respectively. The binding constant $K_{app}$ for LSP was greater than other N-drugs. Furthermore, the suggested method was hence applied for the routine detection of the concentration of N-drugs in bulk and tablet or syrup dosage forms. FTIR analysis and the electron-mapping density provided the chemical affinity of N-drugs towards EY. Full article

Molnupiravir is an antiviral drug against viral RNA polymerase activity approved by the FDA for the treatment of COVID-19, which is metabolized to β-D-N4-hydroxycytidine (NHC) in human blood plasma. A novel method was developed and validated for quantifying NHC in human plasma within the analytical range of 10–10,000 ng/mL using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) to support pharmacokinetics studies. For sample preparation, the method of protein precipitation by acetonitrile was used, with promethazine as an internal standard. Chromatographic separation was carried out on a Shim-pack GWS C18 (150 mm × 4.6 mm, 5 μm) column in a gradient elution mode. A 0.1% formic acid solution in water with 0.08% ammonia solution (eluent A, v/v) and 0.1% formic acid solution in methanol with 0.08% ammonia solution mixed with acetonitrile in a 4:1 ratio (eluent B, v/v) were used as a mobile phase. Electrospray ionization (ESI) was used as an ionization source. The developed method was validated in accordance with the Eurasian Economic Union (EAEU) rules, based on the European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines for the following parameters and used within the analytical part of the clinical study of molnupiravir drugs: selectivity, suitability of standard sample, matrix effect, calibration curve, accuracy, precision, recovery, lower limit of quantification (LLOQ), carryover, and stability. Full article

This study aimed to determine promethazine (PMZ) and its metabolites, promethazine sulfoxide (PMZSO) and monodesmethyl-promethazine (Nor₁PMZ), in swine muscle, liver, kidney, and fat. A sample preparation method and high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis were established and validated. The samples were extracted using 0.1% formic acid–acetonitrile and purified with acetonitrile-saturated n-hexane. After concentration by rotary evaporation, the extract was re-dissolved in a mixture of 0.1% formic acid-water and acetonitrile (80:20, v/v). Analysis was performed using a Waters Symmetry C₁₈ column (100 mm × 2.1 mm i.d., 3.5 μm) with 0.1% formic acid–water and acetonitrile as the mobile phase. The target compounds were determined using positive ion scan and multiple reaction monitoring. PMZ and Nor₁PMZ were quantified with deuterated promethazine (PMZ-d6) as the internal standard, while PMZSO was quantified using the external standard method. In spiked muscle, liver, and kidney samples, the limits of detection (LOD) and limits of quantification (LOQ) for PMZ and PMZSO were 0.05 μg/kg and 0.1 μg/kg, respectively, while for Nor₁PMZ, these values were 0.1 μg/kg and 0.5 μg/kg, respectively. For spiked fat samples, the LOD and LOQ for all three analytes were found to be 0.05 μg/kg and 0.1 μg/kg, respectively. The sensitivity of this proposed method reaches or exceeds that presented in previous reports. The analytes PMZ and PMZSO exhibited good linearity within the range of 0.1 μg/kg to 50 μg/kg, while Nor₁PMZ showed good linearity within the range of 0.5 μg/kg to 50 μg/kg, with correlation coefficients (r) greater than 0.99. The average recoveries of the target analytes in the samples varied from 77% to 111%, with the precision fluctuating between 1.8% and 11%. This study developed, for the first time, an HPLC–MS/MS method for the determination of PMZ, PMZSO, and Nor₁PMZ in four swine edible tissues, comprehensively covering the target tissues of monitoring object. The method is applicable for monitoring veterinary drug residues in animal-derived foods, ensuring food safety. Full article

Phlebia radiata is a widespread white-rot basidiomycete fungus with significance in diverse biotechnological applications due to its ability to degrade aromatic compounds, xenobiotics, and lignin using an assortment of oxidative enzymes including laccase. In this work, a chemical screen with 480 conditions was conducted to identify chemical inducers of laccase expression in P. radiata. Among the chemicals tested, phenothiazines were observed to induce laccase activity in P. radiata, with promethazine being the strongest laccase inducer of the phenothiazine-derived compounds examined. Secretomes produced by promethazine-treated P. radiata exhibited increased laccase protein abundance, increased enzymatic activity, and an enhanced ability to degrade phenolic model lignin compounds. Transcriptomics analyses revealed that promethazine rapidly induced the expression of genes encoding lignin-degrading enzymes, including laccase and various oxidoreductases, showing that the increased laccase activity was due to increased laccase gene expression. Finally, the generality of promethazine as an inducer of laccases in fungi was demonstrated by showing that promethazine treatment also increased laccase activity in other relevant fungal species with known lignin conversion capabilities including Trametes versicolor and Pleurotus ostreatus. Full article

Promethazine hydrochloride (PM) is a widely used drug so its determination is important. Solid-contact potentiometric sensors could be an appropriate solution for that purpose due to their analytical properties. The aim of this research was to develop solid-contact sensor for potentiometric determination of PM. It had a liquid membrane containing hybrid sensing material based on functionalized carbon nanomaterials and PM ions. The membrane composition for the new PM sensor was optimized by varying different membrane plasticizers and the content of the sensing material. The plasticizer was selected based on calculations of Hansen solubility parameters (HSP) and experimental data. The best analytical performances were obtained using a sensor with 2-nitrophenyl phenyl ether (NPPE) as the plasticizer and 4% of the sensing material. It had a Nernstian slope (59.4 mV/decade of activity), a wide working range (6.2 × 10⁻⁷ M–5.0 × 10⁻³ M), a low limit of detection (1.5 × 10⁻⁷ M), fast response time (6 s), low signal drift (−1.2 mV/h), and good selectivity. The working pH range of the sensor was between 2 and 7. The new PM sensor was successfully used for accurate PM determination in a pure aqueous PM solution and pharmaceutical products. For that purpose, the Gran method and potentiometric titration were used. Full article

Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the present study, taste masked PMZ nanocapsules (NCs) were prepared using an interfacial polycondensation technique. A one-step approach was used to expedite the synthesis of NCs made from a biocompatible and biodegradable polyamide based on l-arginine. The produced NCs had an average particle size of 193.63 ± 39.1 nm and a zeta potential of −31.7 ± 1.25 mV, indicating their stability. The NCs were characterized using differential scanning calorimetric analysis and X-ray diffraction, as well as transmission electron microscopy that demonstrated the formation of the NCs and the incorporation of PMZ within the polymer. The in vitro release study of the PMZ-loaded NCs displayed a 0.91 ± 0.02% release of PMZ after 10 min using artificial saliva as the dissolution media, indicating excellent taste masked particles. The in vivo study using mice revealed that the amount of fluid consumed by the PMZ-NCs group was significantly higher than that consumed by the free PMZ group (p < 0.05). This study confirmed that NCs using polyamides based on l-arginine and interfacial polycondensation can serve as a good platform for the effective taste masking of bitter actives. Full article

Persistent apical periodontitis occurs when the endodontic treatment fails to eradicate the intraradicular infection, and is mainly caused by Gram-positive bacteria and yeasts, such as Enterococcus faecalis and Candida albicans, respectively. Phenothiazines have been described as potential antimicrobials against bacteria and fungi. This study aimed to investigate the antimicrobial potential of promethazine (PMZ) and chlorpromazine (CPZ) against E. faecalis and C. albicans dual-species biofilms. The susceptibility of planktonic cells to phenothiazines, chlorhexidine (CHX) and sodium hypochlorite (NaOCl) was initially analyzed by broth microdilution. Interaction between phenothiazines and CHX was examined by chequerboard assay. The effect of NaOCl, PMZ, CPZ, CHX, PMZ + CHX, and CPZ + CHX on biofilms was investigated by susceptibility assays, biochemical and morphological analyses. Results were evaluated through one-way ANOVA and Tukey’s multiple comparison post-test. PMZ, alone or in combination with irrigants, was the most efficient phenothiazine, capable of reducing cell counts, biomass, biovolume, carbohydrate and protein contents of dual-species biofilms. Neither PMZ nor CPZ increased the antimicrobial activity of CHX. Further investigations of the properties of phenothiazines should be performed to encourage their use in endodontic clinical practice. Full article

Stroke is a leading threat to human life. Metabolic dysfunction of glucose may play a key role in stroke pathophysiology. Pharmacological hypothermia (PH) is a potential neuroprotective strategy for stroke, in which the temperature is decreased safely. The present study determined whether neuroprotective PH with chlorpromazine and promethazine (C + P), plus dihydrocapsaicin (DHC) improved glucose metabolism in acute ischemic stroke. A total of 208 adult male Sprague Dawley rats were randomly divided into the following groups: sham, stroke, and stroke with various treatments including C + P, DHC, C + P + DHC, phloretin (glucose transporter (GLUT)-1 inhibitor), cytochalasin B (GLUT-3 inhibitor), TZD (thiazolidinedione, phosphoenolpyruvate carboxykinase (PCK) inhibitor), and apocynin (nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor). Stroke was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 6 or 24 h of reperfusion. Rectal temperature was monitored before, during, and after PH. Infarct volume and neurological deficits were measured to assess the neuroprotective effects. Reactive oxygen species (ROS), NOX activity, lactate, apoptotic cell death, glucose, and ATP levels were measured. Protein expression of GLUT-1, GLUT-3, phosphofructokinase (PFK), lactate dehydrogenase (LDH), PCK1, PCK2, and NOX subunit gp91 was measured with Western blotting. PH with a combination of C + P and DHC induced faster, longer, and deeper hypothermia, as compared to each alone. PH significantly improved every measured outcome as compared to stroke and monotherapy. PH reduced brain infarction, neurological deficits, protein levels of glycolytic enzymes (GLUT-1, GLUT-3, PFK and LDH), gluconeogenic enzymes (PCK1 and PCK2), NOX activity and its subunit gp91, ROS, apoptotic cell death, glucose, and lactate, while raising ATP levels. In conclusion, stroke impaired glucose metabolism by enhancing hyperglycolysis and gluconeogenesis, which led to ischemic injury, all of which were reversed by PH induced by a combination of C + P and DHC. Full article

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. Full article

Array-based optical sensing is an efficient technique for the determination and discrimination of small organic molecules. This study is aimed at the development of a simple and rapid strategy for obtaining an optical response from a wide range of low-molecular-weight organic compounds. We have suggested a colorimetric and fluorimetric sensing platform based on the combination of two response mechanisms using carbocyanine dyes: aggregation and oxidation. In the first one, the analyte forms ternary aggregates with an oppositely charged surfactant wherein the dye is solubilized in the hydrophobic domains of the surfactant accompanied with fluorescent enhancement. The second mechanism is based on the effect of the analyte on the catalytic reaction rate of dye oxidation with H₂O₂ in the presence of a metal ion (Cu²⁺, Pd²⁺), which entails fluorescence waning and color change. The reaction mixture in a 96-well plate is photographed in visible light (colorimetry) and the near-IR region under red light excitation (fluorimetry). In this proof-of-concept study, we demonstrated the feasibility of discrimination of nine medicinal compounds using principal component analysis: four cephalosporins (ceftriaxone, cefazolin, ceftazidime, cefotaxime), three phenothiazines (promethazine, promazine, chlorpromazine), and two penicillins (benzylpenicillin, ampicillin) in an aqueous solution and in the presence of turkey meat extract. The suggested platform allows simple and rapid recognition of analytes of various nature without using spectral equipment, except for a photo camera. Full article

The increasing concern about chiral pharmaceutical pollutants is connected to environmental contamination causing both chronic and acute harmful effects on living organisms. The design and application of sustainable surfactants in the remediation of polluted sites require knowledge of partitioning between surfactants and potential pollutants. The interfacial and thermodynamic properties of two gemini surfactants, namely, alkanediyi-α,ω-bis(dimethylhexadecyl ammonium bromide) (16-s-16, where s = 10, 12), were studied in the presence of the inherently biodegradable oxime-functionalized ionic liquid (IL) 4-((hydroxyimino)methyl)-1-(2-(octylamino)-2-oxoethyl)pyridin-1-ium bromide (4-PyC8) in an aqueous solution using surface tension, conductivity, fluorescence, FTIR and ¹H NMR spectroscopic techniques. The conductivity, surface tension and fluorescence measurements indicated that the presence of the IL 4-PyC8 resulted in decreasing CMC and facilitated the aggregation process. The various thermodynamic parameters, interfacial properties, aggregation number and Stern–Volmer constant were also evaluated. The IL 4-PyC8-gemini interactions were studied using DLS, FTIR and NMR spectroscopic techniques. The hydrodynamic diameter of the gemini aggregates in the presence of promethazine (PMZ) as a potential chiral pollutant and the IL 4-PyC8 underwent a transition when the drug was added, from large aggregates (270 nm) to small micelles, which supported the gemini:IL 4-PyC8:promethazine interaction. The structural transitions in the presence of promethazine may be used for designing systems that are responsive to changes in size and shape of the aggregates as an analytical signal for selective detection and binding pollutants. Full article

A drug/proton-antiporter, whose the molecular structure is still unknown, was previously evidenced at the blood-brain barrier (BBB) by functional experiments. The computational method could help in the identification of substrates of this solute carrier (SLC) transporter. Two pharmacophore models for substrates of this transporter using the FLAPpharm approach were developed. The trans-stimulation potency of 40 selected compounds for already known specific substrates ([³H]-clonidine) were determined and compared in the human brain endothelial cell line hCMEC/D3. Results. The two pharmacophore models obtained were used as templates to screen xenobiotic and endogenous compounds from four databases (e.g., Specs), and 45 hypothetical new candidates were tested to determine their substrate capacity. Psychoactive drugs such as antidepressants (e.g., imipramine, desipramine), antipsychotics/neuroleptics such as phenothiazine derivatives (chlorpromazine), sedatives anti-histamine-H₁ drugs (promazine, promethazine, triprolidine, pheniramine), opiates/opioids (e.g., hydrocodone), trihexyphenidyl and sibutramine were correctly predicted as proton-antiporter substrates. The best performing pharmacophore model for the proton-antiporter substrates appeared as a good predictor of known substrates and allowed the identification of new substrate compounds. This model marks a new step in the characterization of this drug/proton-antiporter and will be of great use in uncovering its substrates and designing chemical entities with an improved influx capability to cross the BBB. Full article