Search Results (51)

Pyridine derivatives are widely distributed in nature and have valuable pharmacological properties. The pyridine core can be found in drugs such as sorafenib, zapiclone or prothipendyl. Dipyridothiazines are derivatives of phenothiazines that exhibit valuable anticancer, antioxidant and immunomodulatory activities. In this study, we present the synthesis and preliminary in vitro analysis of anticancer activity towards melanotic (COLO829, G361) and amelanotic (A375, C32) melanoma cells and normal human fibroblasts (HDF) of a series of new tricyclic diazaphenothiazines containing a pyridine scaffold in their structure. The structures of these new molecules was confirmed using spectral techniques, including ¹H NMR, ¹³C NMR, 2D NMR and HRMS. An in vitro panel of experiments was assessed using the WST-1 assay and cytometric techniques. The two most promising compounds were analyzed for their effect on intracellular GSH levels, mitochondrial membrane potential and their ability to initiate DNA fragmentation to determine the potential mechanism of both cytotoxic and proapoptotic activity. The conducted studies confirmed the ability of the new 3-methyl-1,6-diazaphenothiazines to induce apoptosis in cancer cells, especially in terms of inducing initial as well as late-phase apoptosis. Moreover, the studied compounds were found to induce redox imbalance (evidenced by GSH depletion) in the analyzed melanoma cells, which may be an important factor that directs melanoma cells towards cell death signaling pathways. Full article

Nanotechnology is transforming contemporary medicine by providing cutting-edge tools for the treatment and diagnosis of complex disorders. Advanced techniques such as bioimaging and photodynamic therapy (PDT) combine early diagnosis and targeted therapy, offering a more precise approach than conventional treatments. However, a significant obstacle for PDT is the need to selectively deliver photosensitizers to disease sites while minimizing systemic side effects. In this context, mesenchymal stem cells have emerged as promising biological carriers due to their natural tropism towards tumors, low immunogenicity, and their ability to overcome biological barriers. In this study, two push–pull compounds, NPI-PTZ and BTZ-PTZ, phenothiazine derivatives featuring aggregation-induced emission (AIE) abilities, were analyzed. These molecules proved to be excellent fluorescent probes and photosensitizing agents. When administered to human bone marrow-derived multipotent stromal cells (hBM-MSCs) and human adipose multipotent stem cells (hASCs), the compounds were efficiently internalized, maintained a stable fluorescent emission for several days, and showed phototoxicity after irradiation, without inducing major cytotoxic effects under normal conditions. These results highlight the potential of NPI-PTZ and BTZ-PTZ combined with mesenchymal stem cells as theranostic tools, bridging bioimaging and PDT, and suggest new possibilities for advanced therapeutic approaches in clinical applications. Full article

This study investigates the electrochemical oxidation mechanisms of chlorpromazine (CPZ), revealing a novel three-electron oxidation pathway that challenges the traditionally accepted two-electron paradigm, offering new insights into CPZ oxidation pathways. Using an integrated approach combining cyclic voltammetry, bulk electrolysis, UV-Vis, FT-IR, ¹H-NMR spectroscopy, and LC-MS/MS analysis, we demonstrate that CPZ undergoes sequential oxidation processes involving both the phenothiazine core and the tertiary amine-containing side chain. Our results highlight the critical role of side-chain oxidation in forming nor-CPZ sulfoxide, an often-overlooked metabolite, which may influence CPZ’s metabolic and pharmacological behaviour. Spectroelectrochemical data reveal stable intermediate species, providing insight into the structural rearrangements accompanying oxidation. This work offers a detailed mechanistic understanding of CPZ redox behaviour, contributing to improved interpretations of its pharmacological and metabolic properties. Full article

Background: Nowadays, exotoxic substance intake is among the most frequently employed methods of suicide. Self-poisoning is quite common among psychiatric patients treated in hospitals. Psychotropic drugs used for suicide include phenothiazines. Promazine hydrochloride (Talofen©) is an alpha-lytic phenothiazine neuroleptic with a high affinity for histaminergic H1 receptors and a low affinity for dopaminergic D2, serotoninergic 5-HT, alpha1-adrenergic, and muscarinic receptors, which may explain its potent sedative effect. The most common adverse effects include extrapyramidal syndromes, weight gain, orthostatic hypotension, QTc prolongation, convulsions, delirium, and psychosis. Rare adverse events include the potential occurrence of autoimmune syndromes and vasculitis. Methods: We report herein the delayed death of a 59-year-old woman due to cardiocirculatory arrest on an arrhythmic basis in the context of vasculitis of the small pulmonary vessels and prolongation of the QTc interval secondary to voluntary acute intoxication with promazine hydrochloride. Results: The incident occurred in a psychiatric patient with a history of prior self-harming acts. Histological investigations revealed wavy fibers in the heart, a lymphocytic granulocyte infiltrate in the walls of small- and medium-caliber vessels, and spotty perivascular deposition of histiocyte-macrophage cells in the lungs. Immunophenotypic investigations showed the prevalence of CD15+ and T-CD3+ elements, thus identifying a small vessel vasculitis. These findings were consistent with the literature regarding adverse events following the intake of promazine hydrochloride, although vasculitis is rare. Conclusions: Thus, while QTc lengthening and arrhythmic incidents are widely reported events associated with promazine hydrochloride use, the development of a rare condition such as pulmonary vasculitis undoubtedly played a synergistic and decisive stressogenic role in the genesis of the cardiac event, leading to irreversible functional arrest. Full article

This study presents a prototype non-aqueous redox flow battery that advances the capabilities of conventional systems by achieving a wide operational voltage range, high efficiency, and prolonged cycle life. Leveraging the redox pair 10-[2-(2-methoxy ethoxy)ethyl]-10H-phenothiazine and 2-ethylterephthalonitrile, the system delivers a discharge cell voltage ranging from approximately 2.25 V to 1.9 V. To address the economic challenges associated with non-aqueous redox flow batteries, this work explores a cost-efficient design using a symmetric cell architecture and a low-cost, porous separator. To evaluate the feasibility and scalability of this approach, a 2D time-transient reactive transport model is developed, integrating Nernst–Planck electroneutrality principles and porous electrode kinetics. The model is optimized and validated against experimental charge/discharge cycles, accurately predicting voltage behavior. Additionally, the study provides crucial insights into the crossover phenomenon, elucidating the transport dynamics and spatial distribution of active species within the cell. This comprehensive framework establishes a robust foundation for future efforts to scale and optimize non-aqueous redox flow batteries for large-scale energy storage applications, bringing them closer to commercial viability. Full article

Objectives: Cancer remains one of the leading causes of death worldwide, and thus, there is a need for the development of innovative and more effective treatment strategies. The aim of the study was to evaluate two types of nanoparticles—nanospheres and micelles—obtained from PLA-based polymers to discover their potential for delivering four types of phenothiazine derivatives. Methods: The morphology, drug-loading properties, cytocompatibility, hemolytic properties and anticancer activity were analyzed. Results: The micelles exhibited significantly higher drug-loading properties, release process and cytotoxic activity against cancer cells compared to the nanospheres. The micelles containing 5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride with an OH group as a substituent in the 10-position of the quinobenzothiazine ring showed the highest drug-loading content, the most efficient drug release, the lowest hemolytic activity and the most significant cytotoxic effect against HeLa cells. Conclusions: The conducted study enabled the development of a delivery system for the new anticancer compound and showed that the choice of drug carrier has a crucial effect on its cytotoxic potential against cancer cells. Full article

Phenothiazine-based photosensitizers bear the intrinsic potential to substitute various expensive organometallic dyes owing to the strong electron-donating nature of the former. If coupled with a strong acceptor unit and the length of N-alkyl chain is appropriately chosen, they can easily produce high efficiency levels in dye-sensitized solar cells. Here, three novel D-A dyes containing 1H-tetrazole-5-acrylic acid as an acceptor were synthesized by varying the N-alkyl chain length at its phenothiazine core and were exploited in dye-sensitized solar cells. Differential scanning calorimetry showed that the synthesized phenothiazine derivatives exhibited behavior characteristic of molecular glasses, with glass transition and melting temperatures in the range of 42–91 and 165–198 °C, respectively. Based on cyclic and differential pulse voltammetry measurements, it was evident that their lowest unoccupied molecular orbital (LUMO) (−3.01–−3.14 eV) and highest occupied molecular orbital (HOMO) (−5.28–−5.33 eV) values were fitted to the TiO₂ conduction band and the redox energy of I⁻/I₃⁻ in electrolyte, respectively. The experimental results were supported by density functional theory, which was also utilized for estimation of the adsorption energy of the dyes on the TiO₂ and its size. Finally, the compounds were tested in dye-sensitized solar cells, which were characterized based on current–voltage measurements. Additionally, for the compound giving the best photovoltaic response, the efficiency of the DSSCs was optimized by a photoanode modification involving the use of cosensitization and coadsorption approaches and the introduction of a blocking layer. Subsequently, two types of tandem dye-sensitized solar cells were constructed, which resulted in an increase in photovoltaic efficiency to 6.37%, as compared to DSSCs before modifications, with a power conversion value of 2.50%. Full article

The present study investigates the influence of photosensitizer selection and the polymer electrolyte composition on the performance of quasi-solid-state dye-sensitized solar cells (QsDSSCs). Two benchmark ruthenium dyes, N719 and Z907, alongside a novel photoactive phenothiazine dye were used. Each dye was incorporated into a QsDSSC architecture employing poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) as the gel electrolyte matrix, with varying molecular weights, to investigate their impacts on the overall device performance and long-term stability. Our results demonstrated that the N719 dye exhibited the highest power conversion efficiency (PCE), attributed to its strong absorption in the visible spectrum and efficient electron injection into the TiO₂ photoanode. Z907, on the other hand, showed moderate PCE due to its broader absorption profile but slower electron injection kinetics. The phenothiazine dye revealed promising PCE, with tunable absorption properties and efficient charge transfer. Furthermore, the impact of PVDF-HFP polymer gel electrolytes with varying molecular weights on cell stability was explored. The QsDSSC incorporating the PVH80 polymer with the phenothiazine dye exhibited reduced dye desorption, due to the effective dye molecules’ immobilization by the gel matrix, and consequently enhanced long-term stability over 600 h. This comparative study sheds light on the interplay between dye selection, the polymer gel’s properties, and QsDSSCs’ performance. These insights are crucial in designing robust and efficient QsDSSCs for practical applications. Full article

Methylene blue was electropolymerized on the surface of stainless steel 316. The addition of sodium oxalate and working at a pH near 11 allowed us to obtain steel electrodes coated with an electroactive polymer. This polymer shows electrochromic properties like those of the monomer, but also exhibits electroactivity at more positive potentials, which is associated with the active centers in the bridges between monomeric units. A digital video electrochemistry study allowed us to simultaneously quantify, on the one hand, the color changes on the entire surface of the stainless steel and on the other to separate the contribution of the active centers of the phenothiazine ring and of the inter-monomer bonds to the overall polymer response by means of assessing the mean color intensities. A reduction mechanism for the polymer, compatible with the pH variation of the observed electrochemical behavior, was proposed. Full article

In this study, a library of 3,7-di(hetero)aryl-substituted 10-(3-trimethylammoniumpropyl)10H-phenothiazine salts is prepared. These title compounds and their precursors are reversible redox systems with tunable potentials. The Hammett correlation gives a very good correlation of the first oxidation potentials with σ_p parameters. Furthermore, the title compounds and their precursors are blue to green-blue emissive. Screening of the salts reveals for some derivatives a distinct inhibition of several pathogenic bacterial strains (Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Aconetobacter baumannii, and Klebsiella pneumoniae) in the lower micromolar range. Full article

Phenothiazine derivatives are widely studied in various fields such as biology, chemistry, and medicine research because of their pharmaceutical effects. The first compound used successfully in the treatment of psychosis was a phenthiazine derivative, chlorpromazine. Apart from its activity in neurons, chlorpromazine has also been reported to display anticancer and antibacterial properties. In this study, we present the synthesis and research on the activity of A549, MDA, MiaPaCa, PC3, and HCT116 cancer cell lines and of S. aureus, S. epidermidis, E. coli, and P. aeruginosa bacterial strains against a series of new tetracyclic chlorpromazine analogues containing a quinoline scaffold in their structure instead of the benzene ring and various substituents at the thiazine nitrogen. The structure of these novel molecules has been determined by ¹H NMR, ¹³C NMR, and HRMS spectral techniques. The seven most active of the twenty-four new chlorpromazine analogues tested were selected to study the mechanism of cytotoxic action. Their ability to induce apoptosis or necrosis in cancer cells was assessed by flow cytometry analysis. The results obtained confirmed the proapoptotic activity of selected compounds, especially in terms of inducing late apoptosis or necrosis in cancer cell lines A549, MiaPaCa-2, and HCT-116. Furthermore, studies on the induction of cell cycle arrest suggest that the new chlorpromazine analogues exert antiproliferative effects by inducing cell cycle arrest in the S phase and, consequently, apoptosis. Full article

A flow-through biosensor system for the determination of uric acid was developed on the platform of flow-through electrochemical cell manufactured by 3D printing from poly(lactic acid) and equipped with a modified screen-printed graphite electrode (SPE). Uricase was immobilized to the inner surface of a replaceable reactor chamber. Its working volume was reduced to 10 μL against a previously reported similar cell. SPE was modified independently of the enzyme reactor with carbon black, pillar[5]arene, poly(amidoamine) dendrimers based on the p-tert-butylthiacalix[4]arene (PAMAM-calix-dendrimers) platform and electropolymerized 3,7-bis(4-aminophenylamino) phenothiazin-5-ium chloride. Introduction of the PAMAM-calix-dendrimers into the electrode coating led to a fivefold increase in the redox currents of the electroactive polymer. It was found that higher generations of the PAMAM-calix-dendrimers led to a greater increase in the currents measured. Coatings consisted of products of the electropolymerization of the phenothiazine with implemented pillar[5]arene and PAMAM-calix-dendrimers showing high efficiency in the electrochemical reduction of hydrogen peroxide that was formed in the enzymatic oxidation of uric acid. The presence of PAMAM-calix-dendrimer G2 in the coating increased the redox signal related to the uric acid assay by more than 1.5 times. The biosensor system was successfully applied for the enzymatic determination of uric acid in chronoamperometric mode. The following optimal parameters for the chronoamperometric determination of uric acid in flow-through conditions were established: pH 8.0, flow rate 0.2 mL·min⁻¹, 5 U of uricase per reactor. Under these conditions, the biosensor system made it possible to determine from 10 nM to 20 μM of uric acid with the limit of detection (LOD) of 4 nM. Glucose (up to 1 mM), dopamine (up to 0.5 mM), and ascorbic acid (up to 50 μM) did not affect the signal of the biosensor toward uric acid. The biosensor was tested on spiked artificial urine samples, and showed 101% recovery for tenfold diluted samples. The ease of assembly of the flow cell and the low cost of the replacement parts make for a promising future application of the biosensor system in routine clinical analyses. Full article

Phthalocyanines and their double-decker complexes are interesting in designing rotative molecular machines, which are crucial for the development of molecular motors and gears. This study explores the design and synthesis of three bulky phthalocyanine ligands functionalized at the α-positions with phenothiazine or carbazole fragments, aiming to investigate dynamic rotational motions in these sterically hindered molecular complexes. Homoleptic and heteroleptic double-decker complexes were synthesized through the complexation of these ligands with Ce(IV). Notably, Ce^IV(Pc2)₂ and Ce^IV(Pc3)₂, both homoleptic complexes, exhibited blocked rotational motions even at high temperatures. The heteroleptic Ce^IV(Pc)(Pc3) complex, designed to lower symmetry, demonstrated switchable rotation along the pseudo-C₄ symmetry axis upon heating the solution. Variable-temperature ¹H-NMR studies revealed distinct dynamic behaviors in these complexes. This study provides insights into the rotational dynamics of sterically hindered double-decker complexes, paving the way for their use in the field of rotative molecular machines. Full article

The development of new drugs or drug candidates based on the phenothiazine system (10H-dibenzo-[b,e]-1,4-thiazine) is a promising approach in view of the diverse biological activity of this tricyclic system, which is present in traditional drugs (chlorpromazine, thioridazine, trifluoperazine, and trifluopromazine) with antipsychotropic, antihistamine and antimuscarinic activities. In practical medicine, these drugs are used as antagonists of dopamine and other neurotransmitter receptors for the treatment of schizophrenia and bipolar disorders. Ongoing studies on the synthesis and biological screening of various phenothiazine derivatives in recent years have revealed other important biological effects of these compounds, among which their antitumor effects are of great interest. This work reports the synthesis of a novel N-substituted phenothiazine analog bearing a mitochondria-directed cationic group (E)-4-(1H-indol-3-ylvinyl)-pyridinium (F16) linked to the nitrogen atom of the phenothiazine core by a butane bridge. The lipophilic cationic F16 fragment was used as a means to enhance transmembrane transport and selective delivery of the hybrid molecule into the mitochondria of cancer cells. In tests on the BT474 breast cancer cell line, the phenothiazine-F16 hybrid demonstrated significant cytotoxic activity. The cytotoxic effect of the compound was noticeable at a concentration of 5 μM and further increased dose-dependently, leading to complete tumor cell death at a concentration of 50 μM (IC₅₀ 3.3 μM). The F16-derivative of phenotzine showed marked mitochondrial targeting. In experiments on isolated rat liver mitochondria, the tested agent, already at a concentration of 5 μM, significantly decreased the membrane potential of succinate-energized organelles. Increasing the concentration of the phenothiazine hybrid to 20 μM resulted in complete dissipation of the potential. The obtained result of antitumor activity against BT-474 cell culture and significant effect on the reduction of mitochondrial membrane potential allows us to consider phenothiazine-F16 hybrid as a new promising antitumor drug. Full article

A novel voltammetric sensor based on a self-assembled composite formed by native DNA and electropolymerized N-phenyl-3-(phenylimino)-3H-phenothiazin-7-amine has been developed and applied for sensitive determination of doxorubicin, an anthracycline drug applied for cancer therapy. For this purpose, a monomeric phenothiazine derivative has been deposited on the glassy carbon electrode from the 0.4 M H₂SO₄-acetone mixture (1:1 v/v) by multiple potential cycling. The DNA aliquot was either on the electrode modified with electropolymerized film or added to the reaction medium prior to electropolymerization. The DNA entrapment and its influence on the redox behavior of the underlying layer were studied by scanning electron microscopy and electrochemical impedance spectroscopy. The DNA–doxorubicin interactions affected the charge distribution in the surface layer and, hence, altered the redox equilibrium of the polyphenothiazine coating. The voltametric signal was successfully applied for the determination of doxorubicin in the concentration range from 10 pM to 0.2 mM (limit of detection 5 pM). The DNA sensor was tested on spiked artificial plasma samples and two commercial medications (recovery of 90–95%). After further testing on real clinical samples, the electrochemical DNA sensor developed can find application in monitoring drug release and screening new antitumor drugs able to intercalate DNA. Full article