Search Results (20)

The World Health Organization included Cryptococcus neoformans and Cryptococcus gattii in its priority fungal pathogen list due to their high mortality rates and frequent treatment failures. These facts have driven research toward the discovery of new compounds for the treatment of cryptococcosis. In this study, we investigated the therapeutic potential of two complexes, [Cu(phendione)₃](ClO₄)₂·4H₂O (Cu-phendione) and [Ag(phendione)₂]ClO₄ (Ag-phendione), against drug-resistant clinical isolates of C. gattii and C. neoformans. Both complexes demonstrated anti-Cryptococcus activity, with Cu-phendione exhibiting minimum inhibitory concentration (MIC) values of 6.25 μM for C. gattii and 3.125 μM for C. neoformans, while Ag-phendione showed an MIC of 1.56 μM for both Cryptococcus species. Notably, both Cu-phendione and Ag-phendione complexes exhibited enhanced antifungal activity against reference strains of C. neoformans and C. gattii. In silico analysis identified both complexes as highly promising, exhibiting good oral bioavailability, high gastrointestinal absorption, and moderate skin permeability. Moreover, neither complex demonstrated toxicity toward sheep erythrocytes at concentrations up to 62.5 μM, with a selectivity index (SI) exceeding 10 for Cu-phendione and 40 for Ag-phendione. In vivo testing using the Galleria mellonella model demonstrated that both complexes were non-toxic, with 100% larval survival at concentrations up to 1000 μM and SI exceeding 160 following a single administration. Interestingly, larvae exposed to Cu-phendione at concentrations of 15.6–31.25 μM exhibited a significant increase in the density of hemocytes, the immune cells responsible for defense in invertebrates. Furthermore, multiple treatments with 62.5 μM of complexes caused either no larval mortality, hemocyte alterations, or changes in silk production or coloration, indicating a lack of toxicity. These findings suggest that Cu-phendione and Ag-phendione may serve as promising antifungal alternatives against Cryptococcus, with minimal host toxicity. Full article

Using non-classical polyfluorophenyl ligands in Pt(II) complexes and other transition metals such as silver is a promising approach in the search for more effective and safer antitumoral drugs. In this work, a series of chelating N-donor ligands with 1,10-phenanthroline and 4,5-diazafluorene backbones and ketone groups were synthesized (1,10-phenanthroline-5,6-dione, 1; (R/S)-6-hydroxy-6-(2-oxypropyl)-1,10-phenanthroline-5(6H)-one, 2; 4,5-diazafluoren-9-one, 3; 9-hydroxy-9-(2-oxypropyl)-4,5-diazafluorene, 4). The corresponding [Ag(N,N)₂]NO₃ (1Ag–4Ag) and [Pt(C₆F₅)₂(N,N)] (1Pt–4Pt) complexes were prepared. The stability of these complexes in DMSO solution was studied, showing no dissociation over 48 h for almost all complexes, except 3Pt. The compounds were characterized by NMR (¹H, ¹³C, and ¹⁹F), MS, and X-ray diffraction (2, 4, 1Ag, 3Ag, 1Pt, and 3Pt). A study of the cytotoxicity of the compounds in lung carcinoma (A-549) and fetal lung fibroblast (MRC-5) cell lines was performed. Compounds 1, 2, 1Ag, 2Ag, 3Ag, 1Pt, 3Pt, and 4Pt were more active against A-549 cells than cisplatin. Complexes 3Ag and 1Pt showed an acceptable SI and better selectivity than cisplatin, proving that silver(I) complexes and Pt(polyfluorophenyl) complexes are valuable options in searching for new antitumoral drugs. Full article

Electrochemical glucose sensor holds significant promise for the monitoring of blood glucose levels in diabetic patients. In this study, we proposed a novel electrochemical glucose sensor based on 1,10-Phenanthroline-5,6-dione (PD)/Ru(III) as a dual redox mediator. The synergistic effect of PD and Ru(III) was utilized to efficiently facilitate the electron transfer between the enzyme-active center and the electrode. Then, a commercial disposable electrochemical glucose sensor was constructed based on screen-printing electrodes. Experimental results indicated the synergy between PD and Ru(III) provided a promising electron transfer environment for a glucose dehydrogenase (GDH)-catalyzed glucose reaction. The sensor exhibits a linear glucose response range from 0.01 to 38.6 mmol/L, with a limit of detection (LOD) as low as 7.0 µmol/L and a sensitivity of 38 µA·L/(mmol·cm²). The accuracy of the sensor was further validated in spiked recovery tests of human venous blood samples. The glucose recovery rate was between 99.5% and 107%, with a relative standard deviation (RSD) of less than 3.2%. These results demonstrate that our sensor has high potential for commercialization and practical application in glucose monitoring. Full article

The eleven new copper(II) and nickel(II) coordination compounds [Cu(L)Br]₂ (1), [Cu(L)Cl] (2), [Cu(L)NO₃] (3), [Ni(L)Cl] (4), [Ni(HL)₂](NO₃)₂ (5), and [Cu(A)(L)]NO₃, where A is 1,10-phenanthroline (6), 2,2′-bipyridine (7), 3,4-dimethylpyridine (8), 3-methylpyridine (9), pyridine (10) and imidazole (11) were synthesized with 3-(morpholin-4-yl)propane-2,3-dione 4-allylthiosemicarbazone (HL). The new thiosemicarbazone was characterized by NMR and FTIR spectroscopy. All the coordination compounds were characterized by elemental analysis and FTIR spectroscopy. Also, the crystal structures of HL and complexes 1, 6, 7, and 11 were determined using single-crystal X-ray diffraction analysis. Complex 1 has a dimeric molecular structure with two bromide bridging ligands, while 6, 7, and 11 are ionic compounds and comprise monomeric complex cations. The studied complexes manifest antibacterial and antifungal activities and also have an antiradical activity that, in many cases, surpasses the activity of trolox, which is used as a standard antioxidant in medicine. Copper complexes 1–3 have very weak antiradical properties (IC₅₀ > 100 µM), but nickel complexes 4–5 are strong antiradicals with IC₅₀ values lower than that of trolox. The mixed ligand copper complexes with additional ligand of N-heteroaromatic base are superior to complexes without these additional ligands. They are 1.4–5 times more active than trolox. Full article

This paper describes the study of an amperometric glucose biosensor based on an enzymatic biofuel cell consisting of a bioanode and a biocathode modified with the same enzyme—glucose oxidase (GOx). A graphite rod electrode (GRE) was electrochemically modified with a layer of Prussian blue (PB) nanoparticles embedded in a poly(pyrrole-2-carboxylic acid) (PPCA) shell, and an additional layer of PPCA and was used as the cathode. A GRE modified with a nanocomposite composed of poly(1,10-phenanthroline-5,6-dione) (PPD) and gold nanoparticles (AuNPs) entrapped in a PPCA shell was used as an anode. Both electrodes were modified with GOx by covalently bonding the enzyme to the carboxyl groups of PPCA. The developed biosensor exhibited a wide linear range of 0.15–124.00 mM with an R² of 0.9998 and a sensitivity of 0.16 μA/mM. The limit of detection (LOD) and quantification (LOQ) were found to be 0.07 and 0.23 mM, respectively. The biosensor demonstrated exceptional selectivity to glucose and operational stability throughout 35 days, as well as good reproducibility, repeatability, and anti-interference ability towards common interfering substances. The studies on human serum demonstrate the ability of the newly designed biosensor to determine glucose in complex real samples at clinically relevant concentrations. Full article

Two types of low-cost reagentless electrochemical glucose biosensors based on graphite rod (GR) electrodes were developed. The electrodes modified with electrochemically synthesized platinum nanostructures (PtNS), 1,10-phenanthroline-5,6-dione (PD), glucose oxidase (GOx) without and with a polypyrrole (Ppy) layer—(i) GR/PtNS/PD/GOx and (ii) GR/PtNS/PD/GOx/Ppy, respectively, were prepared and tested. Glucose biosensors based on GR/PtNS/PD/GOx and GR/PtNS/PD/GOx/Ppy electrodes were characterized by the sensitivity of 10.1 and 5.31 μA/(mM cm²), linear range (LR) up to 16.5 and 39.0 mM, limit of detection (LOD) of 0.198 and 0.561 mM, good reproducibility, and storage stability. The developed glucose biosensors based on GR/PtNS/PD/GOx/Ppy electrodes showed exceptional resistance to interfering compounds and proved to be highly efficient for the determination of glucose levels in blood serum. Full article

Two ternary copper(II) complexes with an anthraquinone and a N,N-heterocyclic donor, [Cu(dmp)(L)(H₂O)](ClO₄) (1), [Cu(bpy)(L)(dmso)](ClO₄) (2), in which dmp = 2,9-dimethyl-1,10-phenanthroline, bpy = 2,2′-bipyridine, and HL = 1-hydroxyanthracene-9,10-dione were synthesized and fully characterized by conductivity, elemental, and spectral analyses (FTIR and UV-Vis; EPR and ESI-MS). The structure of 1 reveals that Cu(II) is bound to two oxygens of L, two nitrogens of dmp, and a molecule of water in the fifth position. In complex 2.1, Cu(II) is also pentacoordinated with an O-bonded dmso in the axial position. The presence of the heteroleptic complexes in solution was evidenced by ESI-MS, EPR in dmso solution and UV-Vis spectrophotometry. All complexes bind to CT-DNA with affinity constants of approximately 10⁴. Complex 2 can nick plasmid DNA but no cleavage was performed by complex 1. The investigation of DNA interactions by spectrofluorimetry using ethidium bromide (EB) showed that it was displaced from DNA sites by the addition of the complexes. The complexes inhibited the growth of chronic myelogenous leukemia and human squamous carcinoma cells with low IC₅₀ values, complex 1 being the most effective. Full article

The routine monitoring of bacterial populations is crucial for ensuring water quality and safeguarding public health. Thus, an electrochemical sensor based on a 1,10-phenanthroline-5,6-dione-modified electrode was developed and explored for the detection of E. coli. The modified electrode exhibited enhanced NADH oxidation ability at a low potential of 0.1 V, which effectively eliminated the interference from other redox compounds in bacteria. The sensitivity for NADH was 0.222 μA/μM, and the limit of detection was 0.0357 μM. Upon cell lysis, the intracellular NADH was released, and the concentration of E. coli was determined through establishing the relationship between the oxidation current signal and NADH concentration. The performance of the electrochemical sensor in the detection of NADH and E. coli suspensions was validated using the WST-8 colorimetric method. The blank recovery experiment in real water samples exhibited good accuracy, with recovery rates ranging from 89.12% to 93.26% and relative standard deviations of less than 10%. The proposed electrochemical sensor realized the detection of E. coli without the usage of biomarkers, which provides a promising approach for the broad-spectrum detection of microbial contents in complex water environments. Full article

Reagentless electrochemical glucose biosensors were developed and investigated. A graphite rod (GR) electrode modified with electrochemically synthesized dendritic gold nanostructures (DGNs) and redox mediators (Med) such as ferrocenecarboxylic acid (FCA), 1,10-phenathroline-5,6-dione (PD), N,N,N′,N′-tetramethylbenzidine (TMB) or tetrathiafulvalene (TTF) in combination with glucose oxidase (GOx) (GR/DGNs/FCA/GOx, GR/DGNs/PD/GOx, GR/DGNs/TMB/GOx, or GR/DGNs/TTF/GOx) were developed and electrochemically investigated. A biosensor based on threefold-layer-by-layer-deposited PD and GOx (GR/DGNs/(PD/GOx)₃) was found to be the most suitable for the determination of glucose. To improve the performance of the developed biosensor, the surface of the GR/DGNs/(PD/GOx)₃ electrode was modified with polypyrrole (Ppy) for 5 h. A glucose biosensor based on a GR/DGNs/(PD/GOx)₃/Ppy_{(5 h)} electrode was characterized using a wide linear dynamic range of up to 39.0 mmol L⁻¹ of glucose, sensitivity of 3.03 µA mM⁻¹ cm⁻², limit of detection of 0.683 mmol L⁻¹, and repeatability of 9.03% for a 29.4 mmol L⁻¹ glucose concentration. The Ppy-based glucose biosensor was characterized by a good storage stability (τ_1/2 = 9.0 days). Additionally, the performance of the developed biosensor in blood serum was investigated. Full article

Leishmaniasis, caused by protozoa of the genus Leishmania, encompasses a group of neglected diseases with diverse clinical and epidemiological manifestations that can be fatal if not adequately and promptly managed/treated. The current chemotherapy options for this disease are expensive, require invasive administration and often lead to severe side effects. In this regard, our research group has previously reported the potent anti-Leishmania activity of two coordination compounds (complexes) derived from 1,10-phenanthroline-5,6-dione (phendione): [Cu(phendione)₃].(ClO₄)₂.4H₂O and [Ag(phendione)₂].ClO₄. The present study aimed to evaluate the effects of these complexes on leishmanolysin (gp63), a virulence factor produced by all Leishmania species that plays multiple functions and is recognized as a potential target for antiparasitic drugs. The results showed that both Ag-phendione (−74.82 kcal/mol) and Cu-phendione (−68.16 kcal/mol) were capable of interacting with the amino acids comprising the active site of the gp63 protein, exhibiting more favorable interaction energies compared to phendione alone (−39.75 kcal/mol) or 1,10-phenanthroline (−45.83 kcal/mol; a classical gp63 inhibitor) as judged by molecular docking assay. The analysis of kinetic parameters using the fluorogenic substrate Z-Phe-Arg-AMC indicated V_max and apparent K_m values of 0.064 µM/s and 14.18 µM, respectively, for the released gp63. The effects of both complexes on gp63 proteolytic activity were consistent with the in silico assay, where Ag-phendione exhibited the highest gp63 inhibition capacity against gp63, with an IC₅₀ value of 2.16 µM and the lowest inhibitory constant value (K_i = 5.13 µM), followed by Cu-phendione (IC₅₀ = 163 µM and K_i = 27.05 µM). Notably, pretreatment of live L. amazonensis promastigotes with the complexes resulted in a significant reduction in the expression of gp63 protein, including the isoforms located on the parasite cell surface. Both complexes markedly decreased the in vitro association indexes between L. amazonensis promastigotes and THP-1 human macrophages; however, this effect was reversed by the addition of soluble gp63 molecules to the interaction medium. Collectively, our findings highlight the potential use of these potent complexes in antivirulence therapy against Leishmania, offering new insights for the development of effective treatments for leishmaniasis. Full article

Trichomonas vaginalis is responsible for 156 million new cases per year worldwide. When present asymptomatically, the parasite can lead to serious complications, such as development of cervical and prostate cancer. As infection increases the acquisition and transmission of HIV, the control of trichomoniasis represents an important niche for the discovery and development of new antiparasitic molecules. This urogenital parasite synthesizes several molecules that allow the establishment and pathogenesis of infection. Among them, peptidases occupy key roles as virulence factors, and the inhibition of these enzymes has become an important mechanism for modulating pathogenesis. Based on these premises, our group recently reported the potent anti-T. vaginalis action of the metal-based complex [Cu(phendione)₃](ClO₄)₂.4H₂O (Cu-phendione). In the present study, we evaluated the influence of Cu-phendione on the modulation of proteolytic activities produced by T. vaginalis by biochemical and molecular approaches. Cu-phendione showed strong inhibitory potential against T. vaginalis peptidases, especially cysteine- and metallo-type peptidases. The latter revealed a more prominent effect at both the post-transcriptional and post-translational levels. Molecular Docking analysis confirmed the interaction of Cu-phendione, with high binding energy (−9.7 and −10.7 kcal·mol⁻¹, respectively) at the active site of both TvMP50 and TvGP63 metallopeptidases. In addition, Cu-phendione significantly reduced trophozoite-mediated cytolysis in human vaginal (HMVII) and monkey kidney (VERO) epithelial cell lineages. These results highlight the antiparasitic potential of Cu-phendione by interaction with important T. vaginalis virulence factors. Full article

The genus Fonsecaea is one of the etiological agents of chromoblastomycosis (CBM), a chronic subcutaneous disease that is difficult to treat. This work aimed to evaluate the effects of copper(II), manganese(II) and silver(I) complexes coordinated with 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione (phendione) on Fonsecaea spp. Our results revealed that most of these complexes were able to inhibit F. pedrosoi, F. monophora and F. nubica conidial viability with minimum inhibitory concentration (MIC) values ranging from 0.6 to 100 µM. The most effective complexes against F. pedrosoi planktonic conidial cells, the main etiologic agent of CBM, were [Ag(phen)₂]ClO₄ and [Ag₂(3,6,9-tdda)(phen)₄].EtOH, (tdda: 3,6,9-trioxaundecanedioate), displaying MIC values equal to 1.2 and 0.6 µM, respectively. These complexes were effective in reducing the viability of F. pedrosoi biofilm formation and maturation. Silver(I)-tdda-phen, combined with itraconazole, reduced the viability and extracellular matrix during F. pedrosoi biofilm development. Moreover, both silver(I) complexes inhibited either metallo- or aspartic-type peptidase activities of F. pedrosoi as well as its conidia into mycelia transformation and melanin production. In addition, the complexes induced the production of intracellular reactive oxygen species in F. pedrosoi. Taken together, our data corroborate the antifungal action of metal-phen complexes, showing they represent a therapeutic option for fungal infections, including CBM. Full article

Leishmaniasis is a neglected disease caused by protozoa belonging to the Leishmania genus. Notably, the search for new, promising and potent anti-Leishmania compounds remains a major goal due to the inefficacy of the available drugs used nowadays. In the present work, we evaluated the effects of 1,10-phenanthroline-5,6-dione (phendione) coordinated to silver(I), [Ag(phendione)₂]ClO₄ (Ag-phendione), and copper(II), [Cu(phendione)₃](ClO₄)₂·4H₂O (Cu-phendione), as potential drugs to be used in the chemotherapy against Leishmania amazonensis and Leishmania chagasi. The results showed that promastigotes treated with Ag-phendione and Cu-phendione presented a significant reduction in the proliferation rate. The IC₅₀ values calculated to Ag-phendione and Cu-phendione, respectively, were 7.8 nM and 7.5 nM for L. amazonensis and 24.5 nM and 20.0 nM for L. chagasi. Microscopical analyses revealed several relevant morphological changes in promastigotes, such as a rounding of the cell body and a shortening/loss of the single flagellum. Moreover, the treatment promoted alterations in the unique mitochondrion of these parasites, inducing significant reductions on both metabolic activity and membrane potential parameters. All these cellular perturbations induced the triggering of apoptosis-like death in these parasites, as judged by the (i) increased percentage of annexin-positive/propidium iodide negative cells, (ii) augmentation in the proportion of parasites in the sub-G₀/G₁ phase and (iii) DNA fragmentation. Finally, the test compounds showed potent effects against intracellular amastigotes; contrarily, these molecules were well tolerated by THP-1 macrophages, which resulted in excellent selective index values. Overall, the results highlight new selective and effective drugs against Leishmania species, which are important etiological agents of both cutaneous (L. amazonensis) and visceral (L. chagasi) leishmaniasis in a global perspective. Full article

Herein, we report the synthesis, structure and magnetic properties of two mononuclear complexes of general formula [Dy(acac)₃(L)], where L = 2,2-dimethyl-1,3-dioxolo[4,5-f][1,10] phenanthroline (1) or 1,10-phenanthroline-5,6-dione (2), and acac⁻ = acetylacetonate anion. A distorted square-antiprismatic N₂O₆ environment around the central Dy(III) ion is formed by three acetylacetonate anions and a phenanthroline-type ligand. Both complexes display a single-molecule magnet (SMM) behavior at zero applied magnetic field. Modification of the peripheral part of ligands L provide substantial effects both on the magnetic relaxation barrier U_eff and on the quantum tunneling of magnetization (QTM). Ab initio quantum-chemical calculations are used to analyze the electronic structure and magnetic properties. Full article

Ruthenium(II) arene complexes exhibit promising chemotherapeutic properties. In this study, the effect of the counter anion in Ru(II) complexes was evaluated by analyzing the biological effect of two Ru(II) p-cymene derivatives with the 1,10-phenanthroline-5,6-dione ligand of general-formula [(η⁶-arene)Ru(L)Cl][X] X = CF₃SO₃ (JHOR10) and PF₆ (JHOR11). The biological activity of JHOR10 and JHOR11 was examined in the ovarian carcinoma cell line A2780, colorectal carcinoma cell line HCT116, doxorubicin-resistant HCT116 (HCT116-Dox) and in normal human dermal fibroblasts. Both complexes JHOR10 and JHOR11 displayed an antiproliferative effect on A2780 and HCT116 cell lines, and low cytotoxicity in fibroblasts. Interestingly, JHOR11 also showed antiproliferative activity in the HCT116-Dox cancer cell line, while JHOR10 was inactive. Studies in A2780 cells showed that JHOR11 induced the production of reactive oxygen species (ROS) that trigger autophagy and cellular senescence, but no apoptosis induction. Further analysis showed that JHOR11 presented no tumorigenicity, with no effect in the cellular mobility, as evaluated by thye wound scratch assay, and no anti- or pro-angiogenic effect, as evaluated by the ex-ovo chorioallantoic membrane (CAM) assay. Importantly, JHOR11 presented no toxicity in chicken and zebrafish embryos and reduced in vivo the proliferation of HCT116 injected into zebrafish embryos. These results show that these are suitable complexes for clinical applications with improved tumor cell cytotoxicity and low toxicity, and that counter-anion alteration might be a viable clinical strategy for improving chemotherapy outcomes in multidrug-resistant (MDR) tumors. Full article