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Bis-heterocycles were synthesized via a consecutive one-pot process by a Groebke-Blackburn-Bienaymé reaction (GBB-3CR) followed by Copper-catalyzed Alkyne-Azide Cycloaddition (CuAAC) assisted by alternative sustainable energies (ASE) such as ultrasonic and mechanical. These efficient and convergent strategies allowed the inâ situ generation of complex azides functionalized with imidazo[1,2-a]pyridines (IMPs), which was used as a synthetic platform. The target molecules contain two privileged scaffolds in medicinal chemistry: IMPs and the heterocyclic bioisostere of trans-amide bond, the 1,4-disubstituted 1H-1,2,3-triazoles (1,4-DS-1,2,3-Ts).
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BODIPYs have a well-established role in biological sciences as chemosensors and versatile biological markers due to their chemical reactivity, which allows for fine-tuning of their photophysical characteristics. In this work, we combined the unique reactivity of arylazo sulfones with the advantages of a "sunflow" reactor to develop a fast, efficient, and versatile method for the photochemical arylation of BODIPYs and other chromophores. This approach resulted in red-shifted emitting fluorophores due to extended electronic delocalization at the 3- and 5-positions of the BODIPY core. This method represents an advantageous approach for BODIPY functionalization compared to existing strategies.
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The title complex, [Cu(C8H18NO5)Cl] or [Cu(H4bis-tris-)Cl], was obtained starting from the previously reported [Cu(H5bis-tris-)Cl]Cl compound. The deprotonation of the amino-polyol ligand H5bis-tris {[bis-(2-hy-droxy-eth-yl)amino]-tris-(hy-droxy-meth-yl)methane, C8H19NO5} promotes the formation of a very strong O-Hâ¯O inter-molecular hydrogen bond, characterized by an Hâ¯O separation of 1.553â (19)â Å and an O-Hâ¯O angle of 178â (4)°. The remaining hy-droxy groups are also engaged in hydrogen bonds, forming R 2 2(8), R 4 4(16), R 4 4(20) and R 4 4(22) ring motifs, which stabilize the triperiodic supra-molecular network.
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Background and Purpose: Plasmodium falciparum and P. vivax are responsible for most malaria cases in humans in the African Region and the Americas; these parasites have developed resistance to classic antimalarial drugs. On the other hand, previous investigations of the alkyl-linked bis tetrahydro-(2H)-1,3,5-thiadiazine-2-thione (bis-THTT) derivatives compounds show satisfactory results against protozoan parasites such as Trypanosoma cruzi, Trypanosoma vaginalis, Trypanosoma brucei rhodesiense and Leishmania donovani. Therefore, it is possible to see some effect of bis-THTT derivatives on other protozoan parasites, such as Plasmodium. Experimental Approach: This study aimed to perform an in vivo biological evaluation of bis-THTT (JH1 to JH6) derivatives compounds as possible anti-malaria drugs in BALB/c mice infected with Plasmodium berghei ANKA and Plasmodium yoelii 17XL strains. In this work, we evaluated the compounds as potential antimalarial drugs in BALB/c mice infected with Plasmodium strains. Key Results: For each compound, we assess the percentages of parasitemia by smears from tail blood and the humoral response by indirect ELISA test using each compound as an antigen. We also evaluated the B lymphocyte response and the cytotoxicity of the bis-THTT derivatives compounds with MTT cell proliferation assays. Conclusions: Our results show that the bis-THTT derivatives JH2 and JH4 presented effective parasitemia control in mice infected with P. berghei; JH5 and JH6 compounds have similar infection control results as chloroquine in mice infected P. yoelii strain. The evaluation of bis-THTT derivatives compounds in a model of BALB/c mice infected with P. berghei and P. yoelii allowed us to conclude that some of them have an antimalarial effect; however, none of the tested compounds exceeded the efficiency of chloroquine.
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During the preparation of fixed prosthesis (including individual bridges and crowns) it is important to select the materials that have the best features and properties to predict a successful clinical treatment. The objective of this study was to determine if the chemical and structural characteristics could cause to increase the fracture resistance, we used four bis-acryl resins Luxatemp, Protemp, Structur and Telio. Three-points bending by Flexural test were performed in ten bars and they were carried out to compare with Anova test. In addition, the bis-acryl resins were analyzed by scanning electron microscopy, to analyze microstructure and morphology and the molecular structure were performed by Infrared Spectroscopy through Attenuated Total Reflectance. A higher flexural strength was found in Luxatemp and Structur with, no significant differences between this study groups. Regarding Protemp and Telio, these study groups showed a lower flexural strength when were compared with Luxatemp and Structur. These results corroborate SEM and ATR analysis because Luxatemp sample showed a regular size particle on the surface and chemically presents a long cross-linkage polymer chain. The presence of CO3, SiO2 and N-H groups as a fillers particle interacting with OH groups cause a higher flexural strength compared with another groups.
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The present study was to evaluate the effect of trace minerals (Zn, Mn, and Cu) from complexed amino acid minerals (ZMCAA) and bis-glycinate chelated minerals (ZMCGly) in laying hen diets on performance, internal and external egg quality, yolk mineral deposition, intestinal morphometry, and bone characteristics. From 78 to 98 weeks of age, 400 White LSL-Lite strain laying hens were distributed in a randomized design with 4 treatments with 10 replicates per treatment. Treatments were distributed in a 2 × 2 factorial arrangement using either Zn, Mn, and Cu of ZMCAA or ZMCGly source at 2 levels: low (20, 20, and 3.5 mg/kg of Zn, Mn, and Cu, respectively) or high (40, 40, and 7 mg/kg of Zn, Mn, and Cu, respectively). The analysis of variance was performed, and in cases where differences were observed, the means were compared using Tukey's test (P < 0.05). The source and level of trace mineral supplementation had a significant impact on the performance of laying hens. Hens fed ZMCAA had higher egg production (P = 0.01), egg weight (P = 0.02), egg mass (P = 0.01), and lower feed conversion ratio (P = 0.05) compared to those fed ZMCGly. The ZMCAA supplementation showed higher albumen height (P = 0.01), albumen weight (P = 0.01), and eggshell thickness (P < 0.01). The deposition of Zn (P < 0.01), Mn (P < 0.01), and Cu (P < 0.01) in the egg yolk was greater for hens received ZMCAA. Tibia weight (P = 0.04) and bone densitometry (P < 0.01) in the tibia were higher with ZMCAA supplementation. In the small intestine, ZMCAA resulted in longer villi (P = 0.02) and shorter crypt depth (P = 0.01) in the duodenum. Jejunum and ileum measurements were influenced by the level and source of trace minerals (P < 0.05). Laying hens fed ZMCAA exhibited superior performance, egg quality, deposition of trace minerals in the egg yolk, and bone density compared to hens fed ZMCGly. In this study, older laying hens supplemented with ZMCAA at lower levels demonstrated adequate levels of supplementation.
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Background: The Behavioral Inhibition System (BIS) comprises limbic circuitry implicated in avoidance behaviors. Its increased activation has been identified as a risk factor for anxiety and depressive disorders. In addition, both Catechol-O-Methyltransferase (COMT) and Brain Derived Neurotrophic Factor (BDNF) have been postulated as candidate genes that constitute a vulnerability for the onset of anxiety and depressive disorders. The aim of this study was to evaluate the possible association between the rs4680 polymorphism of the COMT gene and the rs6265 polymorphism of the BDNF gene with the BIS and the Behavioral Activation System (BAS) in a population sample from Colombia. Methods: Genetic information was obtained by extracting DNA from blood samples of 80 participants and using Taqman probes designed for each polymorphism. In addition, participants completed a BIS/BAS scale in order to establish a neuropsychological classification. Results: The frequency of the Met allele of the BDNF gene was greater in the group with BIS sensitivity compared to the group with BAS sensitivity. On the contrary, the frequency of the Met allele of the COMT gen did not show a significant association with the BIS. Conclusions: The rs6265 polymorphism of BDNF gene is associated with the BIS which in turn constitutes a risk factor for anxiety and depression.
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INTRODUCTION: Hemodialysis is life-sustaining in kidney failure. However, proper regulation of body fluids depends on an accurate estimate of target weight. This trial aims to compare clinical endpoints between target weight estimation guided by bioimpedance spectroscopy and usual care in hemodialysis patients. METHODS: This is an open-label, parallel-group, controlled trial that randomized, through a table of random numbers, adult patients on maintenance hemodialysis to target weight estimation based on monthly clinical evaluation alone or added to evaluation by bioimpedance twice a year. The primary outcome was survival, and the secondary outcomes were the rate of hospital admissions, change in blood pressure (BP), and antihypertensive drugs load. Participants were followed for 2 years. Survival analysis was performed using Kaplan-Meier estimator and Log-rank test, and hospital admissions were analyzed by the incidence-rate ratio. FINDINGS: One hundred and ten patients were randomized to the usual care (52) or bioimpedance (58) groups, with a mean age of 57.4 (15.4) years, 64 (58%) males. There was no difference between the groups at baseline. Survival was not significantly different between groups (log-rank test p = 0.68), but the trial was underpowered for this outcome. There was also no difference between the groups in the change in systolic or diastolic BP or in the number of antihypertensive drugs being used. The incidence rate of hospital admissions was 3.1 and 2.1 per person-year in usual care and bioimpedance groups, respectively, with a time-adjusted incidence rate ratio of 1.48 (95% CI: 1.20-1.82, p = 0.0001) and attributable fraction of risk among exposed individuals of 0.32 (95% CI: 0.17-0.45). DISCUSSION: The inclusion of bioimpedance data to guide the estimation of target weight in hemodialysis patients had no detectable impact on survival or BP control, but significantly reduced the incidence rate of hospital admissions. The study was registered at ClinicalTrials.gov Identifier: NCT05272800.
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Antihipertensivos , Diálisis Renal , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Presión Sanguínea , Hospitales , Incidencia , Diálisis Renal/métodos , AncianoRESUMEN
A series of four novel heteroleptic Cu(I) complexes, bearing bis(1H-indazol-1-yl)methane analogues as N,N ligands and DPEPhos as the P,P ligand, were synthesised in high yields under mild conditions and characterised by spectroscopic and spectrometric techniques. In addition, the position of the carboxymethyl substituent in the complexes and its effect on the electrochemical and photophysical behaviour was evaluated. As expected, the homoleptic copper (I) complexes with the N,N ligands showed air instability. In contrast, the obtained heteroleptic complexes were air- and water-stable in solid and solution. All complexes displayed green-yellow luminescence in CH2Cl2 at room temperature due to ligand-centred (LC) phosphorescence in the case of the Cu(I) complex with an unsubstituted N,N ligand and metal-to-ligand charge transfer (MLCT) phosphorescence for the carboxymethyl-substituted complexes. Interestingly, proper substitution of the bis(1H-indazol-1-yl)methane ligand enabled the achievement of a remarkable luminescent yield (2.5%) in solution, showcasing the great potential of this novel class of copper(I) complexes for potential applications in luminescent devices and/or photocatalysis.
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Bis(2-carboxyphenyl) succinate (disalicylic acid; DSA) is composed of two salicylic acids connected by a succinyl linker. Here, we propose its use as a new, synthetic plant-protection agent. DSA was shown to control Pectobacterium brasiliense, an emerging soft-rot pathogen of potato and ornamental crops, at minimal inhibitory concentrations (MIC) lower than those of salicylic acid. Our computational-docking analysis predicted that DSA would inhibit the quorum-sensing (QS) synthase of P. brasiliense ExpI more strongly than SA would. In fact, applying DSA to P. brasiliense inhibited its biofilm formation, secretion of plant cell wall-degrading enzymes, motility and production of acyl-homoserine lactones (AHL) and, subsequently, impaired its virulence. DSA also inhibited the production of AHL by a QS-negative Escherichia coli strain (DH5α) that had been transformed with P. brasiliense AHL synthase, as demonstrated by the biosensors Chromobacterium violaceaum CV026 and E. coli pSB401. Inhibition of the QS machinery appears to be one of the mechanisms by which DSA inhibits specific virulence determinants. A new route is proposed for the synthesis of DSA, which holds greater potential for use as an anti-virulence agent than its precursor SA. Based on these findings, DSA is an excellent candidate for repurposing for new applications.
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Trypanosomiasis and leishmaniasis are neglected infections caused by trypanosomatid parasites. The first-line treatments have many adverse effects, high costs, and are prone to resistance development, hence the necessity for new chemotherapeutic options. In line with this, twenty five 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives were synthesized and evaluated in vitro for their anti-trypanosomatid activity. Ten and five compounds from this series showed IC50 ≤ 10 µM against the promastigote and the bloodstream stage of Leishmania mexicana and Trypanosoma brucei brucei, respectively. Overall, derivatives with pyrazole rings substituted with electron-withdrawing groups proved more active than those with electron-donating groups. The hits proved moderately selective towards L. mexicana and T. brucei (selectivity index, SI, compared to murine macrophages = 5−26). The exception was one derivative displaying an SI (>111−189) against T. brucei that surpassed, by >6-fold, the selectivity of the clinical drug nifurtimox (SI = 13−28.5). Despite sharing a common scaffold, the hits differed in their mechanism of action, with halogenated derivatives inducing a rapid and marked intracellular oxidative milieu in infective T. brucei. Notably, most of the hits presented better absorption, distribution, metabolism, and excretion (ADME) properties than the reference drugs. Several of the bioactive molecules herein identified represent a promising starting point for further improvement of their trypanosomatid potency and selectivity.
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The unprecedented mononucleated ligand (6,6-di(1H-indol-3-yl)-N,N-bis(pyridin-2-ylmethyl)hexan-1-amine (LC5) with an N3-donor set and its complexes [Zn(LC5)Cl2] ⢠2CH3OH (1) and [Zn(LC5)2](ClO4)2 (2), were successfully prepared. All compounds were fully characterized by a suite of physicochemical methods. Fluid 1H and 13C NMR spectroscopy, as well as DFT and TD-DFT calculations, were carried out to propose a viable structural arrangement for both complexes. The interaction between these compounds and DNA was monitored in the UV region where binding constants (Kb) were estimated (2 > 1 > LC5). These data were corroborated by DNA cleavage assays using groove binders, circular dichroism, and docking studies. Both complexes confirmed their biocide activity against selected microorganisms: Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria, the filamentous fungi A. fumigatus and S. cerevisiae. Finally, the cytotoxic activities of 1 and 2 were tested against the erythroleukemia K562 cell line. For all biological studies, it was probed that the presence of the indole moieties and the zinc atoms in the chemical composition of the complexes studied could increase the magnitude of the activity following the order: 2 > 1 > LC5, where a linear relationship between the biological activity upon K562 cells (IC50) and DNA binding studies (Kb) was found.
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Complejos de Coordinación , Desinfectantes , Aminas , Complejos de Coordinación/química , ADN/química , Escherichia coli/metabolismo , Indoles/farmacología , Ligandos , Metano , Saccharomyces cerevisiae/metabolismo , Staphylococcus aureus/metabolismo , Zinc/químicaRESUMEN
We report herein the synthesis and application of enantiopure C2 -symmetric primary amine-1,3-bis-thiourea organocatalysts in enantioselective conjugate 1,4-Michael addition of carbonyl containing nucleophiles, to nitroalkenes and N-phenylmaleimide, leading to final products in good enantioselectivities (up to 99%) and yields (up to 99%). We propose supramolecular noncovalent interactions within the organocatalyst's cleft between the substrate and the catalyst, via hydrogen bonding. Supramolecular interaction thus lowers the transition state energy mimicking an enzyme. Mechanism underlying our experimental results is supported by theorical calculations.
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Alquenos , Tiourea , Alquenos/química , Catálisis , Nitrocompuestos/química , Estereoisomerismo , Tiourea/químicaRESUMEN
BACKGROUND: Photodynamic therapy (PDT) activates a photosensitizer by visible light to generate cytotoxic oxygen species that lead to cell death. With proper illumination, PDT is often used in applications on superficial and sub-surface lesions. Sporotrichosis infection occurs by Sporothrix fungi which causes a skin wound, worsened by Candida albicans infections. This study investigated the photosensitizing efficiency of the Ru(phen)2(pPDIp)(PF6)2 complex, RupPDIp, against S. brasiliensis and C. albicans. MATERIAL AND METHODS: RupPDIp efficiency against these fungi was tested using 450 nm (blue light and 36 J/cm2) and 525 nm (green light, 25.2 J/cm2) at 0.05-20 µM concentrations. To ensure PDT effectiveness, control groups were tested in the absence and in the presence of RupPDIp under light irradiation and in the dark. RESULTS: RupPDIp eliminated both fungi at ≤5.0 µM. Green light showed the best results, eliminating S. brasiliensis and C. albicans colonies at RupPDIp 0.5 µM and 0.05 µM, respectively. CONCLUSION: RupPDIp is a promising photosensitizer in aPDT, eliminating 106 CFU/mL of both fungi at 450 nm and 525 nm, with lower light doses and concentrations when treated with the green light compared to the blue light.
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Antiinfecciosos , Fotoquimioterapia , Sporothrix , Antiinfecciosos/uso terapéutico , Candida albicans/efectos de la radiación , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
The thermochemical study of the 1,3-bis(N-carbazolyl)benzene (NCB) and 1,4-bis(diphenylamino)benzene (DAB) involved the combination of combustion calorimetric (CC) and thermogravimetric techniques. The molar heat capacities over the temperature range of (274.15 to 332.15) K, as well as the melting temperatures and enthalpies of fusion were measured for both compounds by differential scanning calorimetry (DSC). The standard molar enthalpies of formation in the crystalline phase were calculated from the values of combustion energy, which in turn were measured using a semi-micro combustion calorimeter. From the thermogravimetric analysis (TGA), the rate of mass loss as a function of the temperature was measured, which was then correlated with Langmuir's equation to derive the vaporization enthalpies for both compounds. From the combination of experimental thermodynamic parameters, it was possible to derive the enthalpy of formation in the gaseous state of each of the title compounds. This parameter was also estimated from computational studies using the G3MP2B3 composite method. To prove the identity of the compounds, the 1H and 13C spectra were determined by nuclear magnetic resonance (NMR), and the Raman spectra of the study compounds of this work were obtained.
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The worldwide known and employed spice of Asian origin, turmeric, receives significant attention due to its numerous purported medicinal properties. Herein, we report an optimized synthesis of curcumin and symmetric curcuminoids of aromatic (bisdemethoxycurcumin) and heterocyclic type, with yields going from good to excellent using the cyclic difluoro-boronate derivative of acetylacetone prepared by reaction of 2,4-pentanedione with boron trifluoride in THF (ca. 95%). The subsequent cleavage of the BF2 group is of significant importance for achieving a high overall yield in this two-step procedure. Such cleavage occurs by treatment with hydrated alumina (Al2O3) or silica (SiO2) oxides, thus allowing the target heptanoids obtained in high yields as an amorphous powder to be filtered off directly from the reaction media. Furthermore, crystallization instead of chromatographic procedures provides a straightforward purification step. The ease and efficiency with which the present methodology can be applied to synthesizing the title compounds earns the terms "click" and "unclick" applied to describe particularly straightforward, efficient reactions. Furthermore, the methodology offers a simple, versatile, fast, and economical synthetic alternative for the obtention of curcumin (85% yield), bis-demethoxycurcumin (78% yield), and the symmetrical heterocyclic curcuminoids (80-92% yield), in pure form and excellent yields.
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Curcumina , Curcumina/química , Diarilheptanoides , Dióxido de Silicio , Curcuma/química , Extractos Vegetales/químicaRESUMEN
Objective: To evaluate color and surface gloss stability of bis-acryl resins and resin composites, submitted to artificial staining with cigarette smoke. Material and Methods: Specimens of each material were prepared (n=15). Two resin composites (GrandioSO [RCG], Filtek Supreme [RCZ]) and five bis-acryl resins (Luxatemp Star [BisLUX], Protemp4 [BisPRO], Structor3 [BisSTR], Visalys Temp [BisVIS] and Yprov [BisYPR]) were tested. Initial color was assessed using a spectrophotometer and surface gloss with a glossmeter. Samples were submitted to smoke exposure (10 cigarettes under 8 minutes per cycle). After 3 and 6 cycles, color and gloss were reassessed. Final readings were performed after brush prophylaxis. Data were analyzed using two-way repeated ANOVA and Tukey's test (p<0.05). Results: Differences and interaction of factors (p<0.01) were detected for both color and gloss readings. Resin composites were the least affected by aging, with gloss reduction after prophylaxis. Differences were detected among bis-acryl resins, with better results for BisLUX and BisPRO. BisPRO and BisSTR, showed reduction in gloss after 60 cigarettes, while BisYPR gloss decreased at all evaluated periods. Conclusion: Resin composites are less susceptible to changes after smoke exposure, while bis-acryl resins results are brand-dependent. Prophylaxis negatively influenced the surface gloss of most of the tested materials (AU)
Objetivo: Avaliar a estabilidade de cor e brilho superficial de resinas compostas e bisacrílicas, submetidos ao manchamento artificial por fumaça de cigarro. Material e Métodos: Foram preparados espécimes de cada material (n=15). Duas resinas compostas (GrandioSO [RCG], Filtek Supreme [RCZ]) e cinco resinas bisacrílicas (Luxatemp Star [BisLUX], Protemp4 [BisPRO], Structor3 [BisSTR], Visalys Temp [BisVIS] e Yprov [BisYPR]) foram testados. A cor inicial foi avaliada usando um espectrofotômetro e o brilho de superfície com um medidor de brilho. As amostras foram submetidas à exposição de fumaça de cigarro (10 cigarros com até 8 minutos por ciclo). Após 3 e 6 ciclos, a cor e o brilho foram reavaliados. As leituras finais foram realizadas após a profilaxia escova de robinson. Os dados foram analisados usando de medidas repetidas e teste de Tukey (p<0,05). Resultados: Foram detectadas diferenças e interação de fatores (p<0,01) tanto para leituras de cor quanto para leituras de brilho. As resinas compostas foram as menos afetados pelo envelhecimento, com redução do brilho após a profilaxia. Foram detectadas diferenças entre as resinas bisacrílicas, com melhores resultados para BisLUX e BisPRO. BisPRO e BisSTR, mostraram redução de brilho após 60 cigarros, enquanto que o brilho da BisYPR diminuiu em todos os períodos avaliados. Conclusão: As resinas compostas são as menos suscetíveis a mudanças após a exposição à fumaça, enquanto os resultados das resinas bisacrílicas são dependentes da marca. A profilaxia influenciou negativamente o brilho de superfície da maioria dos materiais testados.(AU)
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Humo , Color , Resinas Compuestas , Restauración Dental ProvisionalRESUMEN
Resumen: La práctica de cirugía robótica es un proceso complejo que implica desarrollo y tecnología no sólo en el campo de la cirugía, sino también en el campo de la anestesiología. Implica un proceso multifactorial, ya que ha generado un cambio drástico multidisciplinario basado en tecnología de punta que pretende ofrecer mejores condiciones durante el manejo perioperatorio en cirugía robótica. La anestesia total intravenosa cumple objetivos específicos en relación a la posición del paciente, relajación cerebral, neuroprotección, hemodinamia, pérdida y recuperación de la conciencia, parálisis neuromuscular, parámetros ventilatorios, etc. Ofrece seguridad y calidad al paciente durante el procedimiento con una mínima interferencia con el monitoreo electrofisiológico y permite modular la profundidad anestésica desde una neurosedación hasta una anestesia general, de acuerdo a las diferentes etapas de la cirugía. Un factor atribuible a la anestesia moderna para el éxito de la cirugía robótica es usar diferentes agentes anestésicos que promuevan inducción, mantenimiento y emersión anestésica más rápida y suave, a fin de reducir el tiempo de recuperación del estado de conciencia, funciones básicas y psicomotoras como la anestesia general multimodal.
Abstract: The practice of robotic surgery is a complex process, involving development and technology; not only in the surgery field but also in the anesthesiology field. It implies a multifactorial process since it has generated a drastic multidisciplinary change based on state-of-the-art technology; which aims to offer better conditions during perioperative management in robotic surgery. Intravenous Total Anesthesia accomplishes specific objectives in relation to patient position, brain relaxation, neuroprotection, hemodynamics, loss and recovery of consciousness, neuromuscular paralysis, ventilatory parameters, providing safety and quality during the procedure; with minimal intervention during electrophysiological monitoring and enabling anesthetic depth to be modulated from neurosedation to general anesthesia, according to the different stages of the surgery. A factor attributable to modern anesthesia for robotic surgery success is to employ different anesthetic agents promoting induction, maintenance of general anesthesia, smother and faster anesthetic emersion, for the purpose of reducing recovery time of the state of consciousness), basic and psychomotor functions; as is the general multimodal anesthesia.
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This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models-S. cerevisiae, five cancer cell lines, and the parasite L. mexicana-were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.
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Antiprotozoarios/síntesis química , Antiprotozoarios/farmacología , Ciclopropanos/síntesis química , Ciclopropanos/farmacología , Leishmaniasis/tratamiento farmacológico , Animales , Antiprotozoarios/química , Antiprotozoarios/uso terapéutico , Línea Celular , Técnicas de Química Sintética , Ciclopropanos/química , Ciclopropanos/uso terapéutico , Diseño de Fármacos , Humanos , Leishmania/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
This paper describes a fast, sensitive, environment-friendly method for the determination of 19 primary aromatic amines (PAAs) in cooking utensils by capillary zone electrophoresis coupled with tandem mass spectrometry. The best electrophoretic separation of PAAs was obtained in 0.1 mol l-1 formic acid (pH 2.4) as the background electrolyte, fused silica capillary (67 cm) with a run time below 6 min. The proposed method presented a linear calibration with correlation coefficients higher than 0.99 and reproducibility in a range of 1-25%. Limits of detection were in the range of 0.2-1.3 µg kg-1 and recoveries were in a range of 85-120% for all the PAAs. The validated method was employed to determine PAAs on 36 samples of cooking utensils using acetic simulant. The results showed that 4,4'-diaminodiphenylmethane and aniline being the most frequently found PAAs in these samples and 28% of cooking utensils were not compliant.