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Screen-printed electrodes (SPEs) are reliable, portable, affordable, and versatile electrochemical platforms for the real-time analytical monitoring of emerging analytes in the environmental, clinical, and agricultural fields. The aim of this study was to evaluate the electrochemical behavior of gold screen-printed electrodes (SPGEs) modified with molecules containing amino (Tr-N) or α-aminophosphonate (Tr-P) groups for the selective and sensitive detection of the toxic metal ions Pb2+ and Hg2+ in aqueous samples. After optimizing the analytical parameters (conditioning potential and time, deposition potential and time, pH and concentration of the supporting electrolyte), anodic square wave stripping voltammetry (SWASV) was used to evaluate and compare the electrochemical performance of bare or modified electrodes for the detection of Hg2+ and Pb2+, either alone or in their mixtures in the concentration range between 1 nM and 10 nM. A significative improvement in the detection ability of Pb2+ ions was recorded for the amino-functionalized gold sensor SPGE-N, while the presence of a phosphonate moiety in SPGE-P led to greater sensitivity towards Hg2+ ions. The developed sensors allow the detection of Pb2+ and Hg2+ with a limit of detection (LOD) of 0.41 nM and 35 pM, respectively, below the legal limits for these heavy metal ions in drinking water or food, while the sensitivity was 5.84 µA nM-1cm-2 and 10 µA nM-1cm-2, respectively, for Pb2+ and Hg2+. The reported results are promising for the development of advanced devices for the in situ and cost-effective monitoring of heavy metals, even in trace amounts, in water resources.
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The one-pot synthesis of N-doped graphene quantum dots (GQDs), capped with a positively charged polyamine (trien), has been realized through a microwave-assisted pyrolysis on solid L-glutamic acid and trien in equimolar amounts. The resulting positively charged nanoparticles are strongly emissive in aqueous solutions and are stable for months. The interaction with the anionic tetrakis(4-sulphonatophenyl)porphyrin (TPPS4) has been investigated at neutral and mild acidic pH using a combination of UV/vis absorption spectroscopy together with static and time-resolved fluorescence emission. At pH = 7, the experimental evidence points to the formation of a supramolecular adduct mainly stabilized by electrostatic interactions. The fluorescence emission of the porphyrin is substantially quenched while GQDs remain still emissive. On decreasing the pH, protonation of TPPS4 leads to formation of porphyrin J-aggregates through the intermediacy of the charged quantum dots.
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Potassium channels have recently emerged as suitable target for the treatment of epileptic diseases. Among potassium channels, KCNT1 channels are the most widely characterized as responsible for several epileptic and developmental encephalopathies. Nevertheless, the medicinal chemistry of KCNT1 blockers is underdeveloped so far. In the present review, we describe and analyse the papers addressing the issue of KCNT1 blockers' development and identification, also evidencing the pros and the cons of the scientific approaches therein described. After a short introduction describing the epileptic diseases and the structure-function of potassium channels, we provide an extensive overview of the chemotypes described so far as KCNT1 blockers, and the scientific approaches used for their identification.
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Química Farmacéutica , Epilepsia , Bloqueadores de los Canales de Potasio , Humanos , Bloqueadores de los Canales de Potasio/química , Bloqueadores de los Canales de Potasio/uso terapéutico , Bloqueadores de los Canales de Potasio/farmacología , Química Farmacéutica/métodos , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Relación Estructura-Actividad , Animales , Anticonvulsivantes/química , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/metabolismo , Canales de Potasio de Dominio Poro en Tándem/antagonistas & inhibidores , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Canales de Potasio de Dominio Poro en Tándem/química , Canales de Potasio con Entrada de Voltaje/antagonistas & inhibidores , Canales de Potasio con Entrada de Voltaje/metabolismo , Canales de potasio activados por SodioRESUMEN
The spread of SARS-CoV-2, along with the lack of targeted medicaments, encouraged research of existing drugs for repurposing. The rapid response to SARS-CoV-2 infection comprises a complex interaction of cytokine storm, endothelial dysfunction, inflammation, and pathologic coagulation. Thus, active molecules targeting multiple steps in SARS-CoV-2 lifecycle are highly wanted. Herein we explored the in silico capability of silibinin from Silybum marianum to interact with the SARS-CoV-2 main target proteins, and the in vitro effects against cytokine-induced-inflammation and dysfunction in human umbilical vein endothelial cells (HUVECs). Computational analysis revealed that silibinin forms a stable complex with SARS-CoV-2 spike protein RBD, has good negative binding affinity with Mpro, and interacts with many residues on the active site of Mpro, thus supporting its potentiality in inhibiting viral entry and replication. Moreover, HUVECs pretreatment with silibinin reduced TNF-α-induced gene expression of the proinflammatory genes IL-6 and MCP-1, as well as of PAI-1, a critical factor in coagulopathy and thrombosis, and of ET-1, a peptide involved in hemostatic vasoconstriction. Then, due to endothelium antiinflammatory and anticoagulant properties of silibinin and its capability to interact with SARS-CoV-2 main target proteins demonstrated herein, silibinin could be a strong candidate for COVID-19 management from a multitarget perspective.
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Células Endoteliales/efectos de los fármacos , Péptido Hidrolasas , SARS-CoV-2 , Silibina , COVID-19 , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Humanos , Simulación del Acoplamiento Molecular , SARS-CoV-2/efectos de los fármacos , Silibina/farmacología , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidoresRESUMEN
The antioxidant activity and the phenolic and α-tocopherol content of 10 Northern Italian mono- and multi-varietal extra virgin olive oils (EVOOs), after early and late olive harvests, was analyzed. A hierarchical cluster analysis was used to evaluate sample similarity. Secoiridoids (SIDs), lignans and flavonoids were the most abundant phenolic compounds identified. The organic Casaliva (among mono-cultivar) and the organic multi-varietal (among blended oils) EVOOs had the higher total phenol content both in early (263.13 and 326.19 mg/kg, respectively) and late harvest (241.88 and 292.34 mg/kg, respectively) conditions. In comparison to late harvest EVOOs, early harvest EVOOs, in particular the organic mono-cultivar Casaliva, showed both higher antioxidant capacity (up to 1285.97 Oxygen Radicals Absorbance Capacity/ORAC units), probably due to the higher SID fraction (54% vs. 40%), and higher α-tocopherol content (up to 280.67 mg/kg). Overall, these results suggest that SIDs and α-tocopherol mainly contribute to antioxidant properties of the studied EVOOs. In light of this, the authors conclude that early harvest, organic mono-cultivar Casaliva EVOO represents the most interesting candidate to explicate healthy effects ascribed to these functional constituents, particularly regarding oxidative stress-related pathologies.
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Antioxidantes/análisis , Análisis de los Alimentos/métodos , Olea/química , Aceite de Oliva/análisis , Cromatografía Líquida de Alta Presión , Flavonoides/análisis , Iridoides/análisis , Italia , Lignanos/análisis , Polifenoles/análisis , Factores de Tiempo , alfa-Tocoferol/análisisRESUMEN
Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune-mediated chronic inflammatory disease, involving mainly the skin, affects about the 2-3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions.
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Aloe/química , Fitoterapia , Psoriasis/tratamiento farmacológico , Administración Cutánea , Humanos , Plantas Medicinales/química , Ensayos Clínicos Controlados Aleatorios como Asunto , Piel/patologíaRESUMEN
1-Indanones have been successfully prepared by means of three different non-conventional techniques, namely microwaves, high-intensity ultrasound and a Q-tube™ reactor. A library of differently substituted 1-indanones has been prepared via one-pot intramolecular Friedel-Crafts acylation and their efficiency and "greenness" have been compared.
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Acilación , Indanos/síntesis química , Estructura Molecular , Indanos/química , Microondas , EstereoisomerismoRESUMEN
Recently, we demonstrated that a Citrus flavanone mix (FM) shows antioxidant and anti-inflammatory activity, even after gastro-duodenal digestion (DFM). The aim of this study was to investigate the possible involvement of the cyclooxygenases (COXs) in the anti-inflammatory activity previously detected, using a human COX inhibitor screening assay, molecular modeling studies, and PGE2 release by Caco-2 cells stimulated with IL-1ß and arachidonic acid. Furthermore, the ability to counteract pro-oxidative processes induced by IL-1ß was evaluated by measuring four oxidative stress markers, namely, carbonylated proteins, thiobarbituric acid-reactive substances, reactive oxygen species, and reduced glutathione/oxidized glutathione ratio in Caco-2 cells. All flavonoids showed a strong inhibitory activity on COXs, confirmed by molecular modeling studies, with DFM, which showed the best and most synergistic activity on COX-2 (82.45% vs. 87.93% of nimesulide). These results were also corroborated by the cell-based assays. Indeed, DFM proves to be the most powerful anti-inflammatory and antioxidant agent reducing, synergistically and in a statistically significant manner (p < 0.05), PGE2 release than the oxidative stress markers, also with respect to the nimesulide and trolox used as reference compounds. This leads to the hypothesis that FM could be an excellent antioxidant and COX inhibitor candidate to counteract intestinal inflammation.
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Pure titanium and titanium alloys are widely used in dentistry and orthopedics. However, despite their outstanding mechanical and biological properties, implant failure mainly due to post-operative infection still remains a significant concern. The possibility to develop inherent antibacterial medical devices was here investigated by covalently inserting bioactive ammonium salts onto the surface of titanium metal substrates. Titanium discs have been functionalized with quaternary ammonium salts (QASs) and with oleic acid (OA), affording the Ti-AEMAC Ti-GTMAC, Ti-AUTEAB, and Ti-OA samples, which were characterized by ATR-FTIR and SEM-EDX analyses and investigated for the roughness and hydrophilic behavior. The chemical modifications were shown to deeply affect the surface properties of the metal substrates and, as a consequence, their bio-interaction. The bacterial adhesion tests against the Gram-negative Escherichia Coli and Gram-positive Staphylococcus aureus, at 1.5 and 24 h of bacterial contact, showed good anti-adhesion activity for Ti-AUTEAB and Ti-OA samples, containing a long alkyl chain between the silicon atom and the ammonium functionality. In particular, the Ti-AUTEAB sample showed inhibition of bacteria adhesion against Escherichia Coli of about one log with respect to the other samples, after 1.5 h. The results of this study highlight the importance of chemical functionalization in addressing the antimicrobial activity of metal surfaces and could open new perspectives in the development of inherent antibacterial medical devices.
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The outbreak of COVID-19 disease caused by SARS-CoV-2, along with the lack of targeted medicaments, forced the scientific world to search for new antiviral formulations. In the current emergent situation, drug repurposing of well-known traditional and/or approved drugs could be the most effective strategy. Herein, through computational approaches, we aimed to screen 14 natural compounds from limonoids and terpenoids class for their ability to inhibit the key therapeutic target proteins of SARS-CoV-2. Among these, some limonoids, namely deacetylnomilin, ichangin and nomilin, and the terpenoid ß-amyrin provided good interaction energies with SARS-CoV-2 3CL hydrolase (Mpro) in molecular dynamic simulation. Interestingly, deacetylnomilin and ichangin showed direct interaction with the catalytic dyad of the enzyme so supporting their potential role in preventing SARS-CoV-2 replication and growth. On the contrary, despite the good affinity with the spike protein RBD site, all the selected phytochemicals lose contact with the amino acid residues over the course of 120ns-long molecular dynamics simulations therefore suggesting they scarcely can interfere in SARS-CoV-2 binding to the ACE2 receptor. The in silico analyses of docking score and binding energies, along with predicted pharmacokinetic profiles, indicate that these triterpenoids might have potential as inhibitors of SARS-CoV-2 Mpro, recommending further in vitro and in vivo investigations for a complete understanding and confirmation of their inhibitory potential.
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COVID-19 , SARS-CoV-2 , Reposicionamiento de Medicamentos , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , TerpenosRESUMEN
OBJECTIVE: To investigate the role of body composition and oxidative stress measured by total thiol groups (TTG) levels in prostate specimens of patients affected by benign prostatic hyperplasia (BPH) or prostate cancer (PCa). PATIENTS AND METHODS: From January 2011 to January 2013, a cohort of 150 consecutive male patients who underwent first prostate biopsy were enrolled. Twelve-core needle biopsy was performed as standard procedure, while twelve more needle tissue cores matched with the previous group were also collected for glutathione determination. After definitive diagnosis, measurement of glutathione was performed in the correspondent one matched prostatic sample where PCa or BPH were identified. A day after the prostatic biopsy, body composition was estimated by air plethysmography (BOD POD®). RESULTS: A significant difference of TTG was observed in BPH and PCa patients; 34 nanomole (nmol) reagent sulfihydrylc (RSH)/ mg protein vs. 1.1 nmol RSH/ mg protein respectively (p<0.05). In BPH patients, a negative correlation was found between TTG and age (r=-0.46; p<0.05), while, in PCa patients, a positive correlation was observed between TTG and fat mass (FM) (r=0.76; p<0.01) and waist circumference (WC) (r=0.49; p<0.05). Multivariate linear regression analysis showed TTG to be negatively associated with age (ß-coefficient=-0.4; p<0.05) in BPH patients and positively with FM (ß-coefficient=3.4; p<0.01) and WC (ß-coefficient=2.7; p<0.05) in PCa patients. CONCLUSION: Aging determines a progressive reduction of TTG in BPH patients, while in PCa subjects glutathione concentrations are significantly lower and FM and WC are associated with an unbalance of its levels.