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1.
Hum Reprod ; 39(5): 1042-1056, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38452349

RESUMEN

STUDY QUESTION: What is the human endometrial non-classical progesterone receptor (PGR) membrane component 2 (PGRMC2) expression pattern throughout the menstrual cycle and what role does it play during decidualization? SUMMARY ANSWER: Endometrial PGRMC2 expression fluctuates during the human menstrual cycle and is abundantly expressed in human endometrial stromal cells (hEnSCs) during in vitro decidualization, process where PGRMC2 is involved in embryo implantation-related pathways. WHAT IS KNOWN ALREADY: The endometrial response to progesterone is mediated by the classical and non-classical PGRs. We previously demonstrated that PGR membrane component 1 (PGRMC1) is critical for endometrial function, embryo implantation, and future placentation, however, the role(s) of PGRMC2, which is structurally similar to PGRMC1, have not been studied in the human endometrium. STUDY DESIGN, SIZE, DURATION: This prospective study comprehensively evaluated the endometrial expression of PGRMC2 throughout the human menstrual cycle and during in vitro decidualization of hEnSCs (isolated from 77 endometrial biopsies that were collected from 66 oocyte donors), using immunohistochemistry, RT-qPCR, western blot, transcriptomic, and proteomic analyses. In addition, functional analysis was carried out to validate the implication of PGRMC2 in hEnSCs during embryo invasion using an in vitro outgrowth model. PARTICIPANTS/MATERIALS, SETTING, METHODS: In vitro decidualization of hEnSCs was induced using co-treatment with cAMP and medroxyprogesterone 17-acetate progestin, and evaluated by measuring prolactin by ELISA and F-actin immunostaining. RT-qPCR was employed to compare expression with other PGRs. To reveal the function of PGRMC2 during the decidualization process, we specifically knocked down PGRMC2 with siRNAs and performed RNA-seq and quantitative proteomics techniques (SWATH-MS). The common differentially expressed genes (DEGs) and proteins (DEPs) were considered for downstream functional enrichment analysis. Finally, to verify its implication in the trophoblast invasion, an outgrowth model was carried out where hEnSCs with silenced PGRMC2 were co-cultured with human trophoblastic spheroids (JEG-3) following in vitro decidualization. MAIN RESULTS AND THE ROLE OF CHANCE: In contrast to PGRMC1 and classical PGRs, endometrial PGRMC2 gene expression was significantly lower during the late- versus mid-secretory phase (P < 0.05). Accordingly, the elevated PGRMC2 protein abundance observed in the endometrial epithelial glands throughout the menstrual cycle dropped in the late secretory phase, when abundance decreased in all endometrial compartments. Nevertheless, PGRMC2 protein increased during the mid-secretory phase in stromal and glandular cells, and PGRMC2 mRNA (P < 0.0001) and protein (P < 0.001) levels were significantly enhanced in the membranes/organelles of decidualized hEnSCs, compared to non-decidualized hEnSCs. Notably, PGRMC1 and PGRMC2 mRNA were significantly more abundant than classical PGRs throughout menstrual cycle phases and in decidualized and non-decidualized hEnSCs (P < 0.05). RNA-seq and proteomics data revealed 4687 DEGs and 28 DEPs, respectively, in decidualized hEnSCs after PGRMC2 silencing. While functional enrichment analysis showed that the 2420 upregulated genes were mainly associated with endoplasmic reticulum function, vesicular transport, morphogenesis, angiogenesis, cell migration, and cell adhesion, the 2267 downregulated genes were associated with aerobic respiration and protein biosynthesis. The protein enrichment analysis showed that 4 upregulated and 24 downregulated proteins were related to aerobic respiration, cellular response, metabolism, localization of endoplasmic reticulum proteins, and ribonucleoside biosynthesis routes. Finally, PGRMC2 knockdown significantly compromised the ability of the decidualized hEnSCs to support trophoblast expansion in an outgrowth model (P < 0.05). LARGE-SCALE DATA: Transcriptomic data are available via NCBI's Gene Expression Omnibus (GEO) under GEO Series accession number GSE251843 and proteomic data via ProteomeXchange with identifier PXD048494. LIMITATIONS, REASONS FOR CAUTION: The functional analyses were limited by the discrete number of human endometrial biopsies. A larger sample size is required to further investigate the potential role(s) of PGRMC2 during embryo implantation and maintenance of pregnancy. Further, the results obtained in the present work should be taken with caution, as the use of a pure primary endometrial stromal population differentiated in vitro does not fully represent the heterogeneity of the endometrium in vivo, nor the paracrine communications occurring between the distinct endometrial cell types. WIDER IMPLICATIONS OF THE FINDINGS: The repression of endometrial PGRMC2 during the late- versus mid-secretory phase, together with its overexpression during decidualization and multiple implications with embryo implantation not only highlighted the unknown roles of PGRMC2 in female reproduction but also the potential to exploit PGRMC2 signaling pathways to improve assisted reproduction treatments in the future. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by Instituto de Salud Carlos III (ISCIII) granted to F.D. (PI20/00405 and PI23/00860), co-funded by the European Union. Y.M.-L. was supported by a predoctoral research grant from Generalitat Valenciana (ACIF/2019/262). R.G.-M. was supported by Generalitat Valenciana (CIAPOT/2022/15). P.d.C. was supported by a predoctoral grant for training in research into health (PFIS FI20/00086) from the Instituto de Salud Carlos III. I.D.-H. was supported by the Spanish Ministry of Science, Innovation and Universities (FPU18/01550). A.P. was supported by the Instituto de Salud Carlos III (PFIS FI18/00009). This research was also supported by IVI Foundation-RMA Global (1911-FIVI-103-FD). The authors declare no conflict of interest.


Asunto(s)
Decidua , Implantación del Embrión , Endometrio , Proteínas de la Membrana , Ciclo Menstrual , Receptores de Progesterona , Células del Estroma , Humanos , Femenino , Endometrio/metabolismo , Endometrio/citología , Receptores de Progesterona/metabolismo , Ciclo Menstrual/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Decidua/metabolismo , Implantación del Embrión/fisiología , Células del Estroma/metabolismo , Adulto , Estudios Prospectivos
2.
Int J Mol Sci ; 25(2)2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38256043

RESUMEN

Hydrosalpinx is a fluid occlusion and distension of the fallopian tubes, often resulting from pelvic inflammatory disease, which reduces the success of artificial reproductive technologies (ARTs) by 50%. Tubal factors account for approximately 25% of infertility cases, but their underlying molecular mechanisms and functional impact on other reproductive tissues remain poorly understood. This proteomic profiling study applied sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) to study hydrosalpinx cyst fluid and pre- and post-salpingectomy endometrial fluid. Among the 967 proteins identified, we found 19 and 17 candidate biomarkers for hydrosalpinx in pre- and post-salpingectomy endometrial fluid, respectively. Salpingectomy significantly affected 76 endometrial proteins, providing insights into the enhanced immune response and inflammation present prior to intervention, and enhanced coagulation cascades and wound healing processes occurring one month after intervention. These findings confirmed that salpingectomy reverses the hydrosalpinx-related functional impairments in the endometrium and set a foundation for further biomarker validation and the development of less-invasive diagnostic strategies for hydrosalpinx.


Asunto(s)
Enfermedad Inflamatoria Pélvica , Proteómica , Femenino , Humanos , Proyectos Piloto , Trompas Uterinas , Endometrio
3.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732152

RESUMEN

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in the early diagnosis and prediction of CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on 12 November 2023, using the MeSH terms "Children", "CPB", "L-FABP", and "Acute Kidney Injury". Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p < 0.05. Of 508 studies assessed, nine were included, comprising 1658 children, of whom 561 (33.8%) developed CPB-AKI. Significantly higher uL-FABP levels in AKI versus non-AKI patients first manifested at baseline to 6 h post-CPB. At 6 h, uL-FABP correlated with CPB duration (r = 0.498, p = 0.036), postoperative serum creatinine (r = 0.567, p < 0.010), and length of hospital stay (r = 0.722, p < 0.0001). Importantly, uL-FABP at baseline (AUC = 0.77, 95% CI: 0.64-0.89, n = 365), 2 h (AUC = 0.71, 95% CI: 0.52-0.90, n = 509), and 6 h (AUC = 0.76, 95% CI: 0.72-0.80, n = 509) diagnosed CPB-AKI earlier. Hence, higher uL-FABP levels associate with worse clinical parameters and may diagnose and predict CPB-AKI earlier.


Asunto(s)
Lesión Renal Aguda , Biomarcadores , Puente Cardiopulmonar , Proteínas de Unión a Ácidos Grasos , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/sangre , Puente Cardiopulmonar/efectos adversos , Proteínas de Unión a Ácidos Grasos/orina , Proteínas de Unión a Ácidos Grasos/sangre , Biomarcadores/orina , Niño , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Complicaciones Posoperatorias/orina , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Preescolar
4.
Bioorg Med Chem ; 94: 117479, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37769443

RESUMEN

Chronic diseases such as cystic fibrosis, inflammatory bowel diseases, rheumatoid arthritis, and cardiovascular illness have been linked to a decrease in selenium levels and an increase in oxidative stress. Selenium is an essential trace element that exhibits antioxidant properties, with selenocysteine enzymes like glutathione peroxidase being particularly effective at reducing peroxides. In this study, a series of synthetic organoselenium compounds were synthesized and evaluated for their potential antioxidant activities. The new selenohydantoin molecules were inspired by selenoneine and synthesized using straightforward methods. Their antioxidant potential was evaluated and proven using classical radical scavenging and metal-reducing methods. The selenohydantoin derivatives exhibited glutathione peroxidase-like activity, reducing hydroperoxides. Theoretical calculations using Density Functional Theory (DFT) revealed the selenone isomer to be the only one occurring in solution, with selenolate as a possible tautomeric form in the presence of a basic species. Cytocompatibility assays indicated that the selenohydantoin derivatives were non-toxic to primary human aortic smooth muscle cells, paving the way for further biological evaluations of their antioxidant activity. The results suggest that selenohydantoin derivatives with trifluoro-methyl (-CF3) and chlorine (-Cl) substituents have significant activities and could be potential candidates for further biological trials. These compounds may contribute to the development of effective therapies for chronic diseases such cardiovascular diseases.

5.
Rev Panam Salud Publica ; 47: e74, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37089787

RESUMEN

Objectives: To assess the accumulated knowledge of the effects of public health emergencies of international concern on disease control and local health systems, and contribute to a better understanding of their effects on health programs and systems. Methods: This was a systematic review of published and gray literature (in English, Portuguese, or Spanish). Electronic databases (BVS/LILACS, PubMed, and SciELO) and Google Scholar were searched. Search terms were: COVID-19 OR H1N1 OR Ebola OR Zika OR poliomyelitis AND (outbreaks OR epidemics) AND (public health systems OR public health surveillance). Results: A total of 3 508 studies were retrieved, of which 31 met the inclusion criteria. The studies addressed the effects of the emergencies on: communicable diseases notification systems; malaria, HIV/AIDS, tuberculosis, poliomyelitis, and malaria surveillance, control, and treatment; microcephaly; dengue; and vaccinations. The populations affected by the emergencies experienced reduced health services, which included fewer health visits, failures in the diagnostic chain, decrease in vaccination, and increased incidence or underreporting of notifiable diseases. Conclusions: Socioeconomic inequity is a determinant of the effects of public health emergencies of international concern within affected populations. The diversion of resources and attention from health authorities disproportionately affects vulnerable populations and can lead, over time, to a weakening of health systems. The analysis of the effects of public health emergencies is important for the development of new protocols that can better respond to future crises.

6.
Int J Mol Sci ; 24(18)2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37762126

RESUMEN

Dopamine is synthesized in the nervous system where it acts as a neurotransmitter. Dopamine is also synthesized in a number of peripheral organs as well as in several types of cells and has organ-specific functions and, as demonstrated more recently, is involved in the regulation of the immune response and inflammatory reaction. In particular, the renal dopaminergic system is very important in the regulation of sodium transport and blood pressure and is particularly sensitive to stimuli that cause oxidative stress and inflammation. This review is focused on how dopamine is synthesized in organs and tissues and the mechanisms by which dopamine and its receptors exert their effects on the inflammatory response.


Asunto(s)
Dopamina , Inflamación , Humanos , Presión Sanguínea , Transporte Iónico , Radiofármacos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
7.
Clin Sci (Lond) ; 136(16): 1205-1227, 2022 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-35979889

RESUMEN

Systemic arterial hypertension is one of the leading causes of morbidity and mortality in the general population, being a risk factor for many cardiovascular diseases. Although its pathogenesis is complex and still poorly understood, some systems appear to play major roles in its development. This review aims to update the current knowledge on the interaction of the intrarenal renin-angiotensin system (RAS) and dopaminergic system in the development of hypertension, focusing on recent scientific hallmarks in the field. The intrarenal RAS, composed of several peptides and receptors, has a critical role in the regulation of blood pressure (BP) and, consequently, the development of hypertension. The RAS is divided into two main intercommunicating axes: the classical axis, composed of angiotensin-converting enzyme, angiotensin II, and angiotensin type 1 receptor, and the ACE2/angiotensin-(1-7)/Mas axis, which appears to modulate the effects of the classical axis. Dopamine and its receptors are also increasingly showing an important role in the pathogenesis of hypertension, as abnormalities in the intrarenal dopaminergic system impair the regulation of renal sodium transport, regardless of the affected dopamine receptor subtype. There are five dopamine receptors, which are divided into two major subtypes: the D1-like (D1R and D5R) and D2-like (D2R, D3R, and D4R) receptors. Mice deficient in any of the five dopamine receptor subtypes have increased BP. Intrarenal RAS and the dopaminergic system have complex interactions. The balance between both systems is essential to regulate the BP homeostasis, as alterations in the control of both can lead to hypertension.


Asunto(s)
Hipertensión , Sistema Renina-Angiotensina , Animales , Presión Arterial , Presión Sanguínea , Dopamina/metabolismo , Dopamina/farmacología , Humanos , Riñón/metabolismo , Ratones , Receptores Dopaminérgicos/metabolismo , Renina/metabolismo , Sistema Renina-Angiotensina/fisiología
8.
J Org Chem ; 87(16): 11007-11020, 2022 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-35926126

RESUMEN

A synthetic protocol for the preparation of α-acyl aminocarboxamides and α-amino amidines is proposed. The selectivity toward each of these two possible products was tuned by simple modifications of the reaction conditions. A broad scope is presented, allowing access to the desired products in up to 87% (Ugi adduct) and 93% (α-amino amidine). Theoretical calculations were carried out, and the analysis led to the proposal of a new mechanistic pathway for the Ugi reaction, in which methanol acts not only as the solvent but also as a reagent. High-resolution (tandem) mass spectrometry experiments allowed the detection and characterization of the key intermediate associated with this new and alternative reaction pathway, thus supporting the theoretical proposal.


Asunto(s)
Amidinas , Solventes
9.
J Org Chem ; 87(5): 2809-2820, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-35108004

RESUMEN

A transition metal-free protocol for the preparation of fluorescent and non-fluoresent 3-methylthio-4-arylmaleimides in a single step through a new rearrangement from thiazolidine-2,4-diones is described. By employing the optimized reaction conditions, a broad scope of derivatives was prepared in ≤97% yield. The reaction tolerated several substituted aryl groups, including the challenging preparation of pyridyl-containing derivatives. A series of control experiments strongly suggested that the new rearrangement involves a key isocyanate intermediate and a further reaction with in situ-generated methylthiomethyl acetate. The photophysical properties of some of the synthesized derivatives as well as their use in live cell imaging were also investigated, revealing that some of the substituted maleimides are capable of selectively staining different regions of the cells.


Asunto(s)
Maleimidas
10.
Pediatr Nephrol ; 37(3): 499-508, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34686915

RESUMEN

BACKGROUND: IgA nephropathy (IgAN) is one of the most prevalent primary glomerulopathies in children. There are various studies investigating the efficacy of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in adults with IgAN. However, only few studies evaluated the efficacy of these medications in pediatric patients. OBJECTIVE: To evaluate the efficacy and safety of ACEI/ARB in children with IgAN. DATA SOURCES: Databases including PubMed, Web of Science, Cochrane, Scopus, and Google Scholar were searched between the 1st of April and 20th of July of 2021 using the keywords "IgA Nephropathy," "Berger's Disease," "Angiotensin-Converting Enzyme Inhibitors," "Angiotensin Receptor Antagonists," "Angiotensin II Type 1 Receptor Blockers," and similar entry terms collected from the Medical Subject Headings (MeSH). STUDY ELIGIBILITY CRITERIA: Observational studies (case series, case-control, cohort, and cross-sectional) and clinical trials with descriptions of pediatric patients (under 19 years old) with histopathological diagnosis of IgA nephropathy and who received ACEI and/or ARB. PARTICIPANTS AND INTERVENTIONS: Pediatric patients (under 19 years old) with histopathological diagnosis of IgA nephropathy and who received ACEI and/or ARB. STUDY APPRAISAL: For quality assessment, the Risk of Bias 2 tool (RoB 2), the Risk Of Bias In Non-randomized Studies of Interventions tool (ROBINS-I), the National Institutes of Health (NIH) quality assessment tool, and the Newcastle-Ottawa Scale (NOS) were used. RESULTS: After recovering 1,471 studies, only eight, published between 2003 and 2019, met the eligibility criteria and were included in this systematic review. Of the 737 included children in the studies, 202 (25.8%) used ACEI/ARB and were compared with placebo and other therapy regimens. Of the seven studies that evaluated proteinuria, six reported an efficacy of ACEI/ARB in reducing this marker. ACEI/ARB also showed a possible effect in reducing hematuria and oxidative stress. The most common side effect was dizziness. LIMITATIONS: The number of studies about the treatment with ACEI/ARB in children with IgAN is scarce. In addition, the studies are very heterogeneous. There are few studies that compared ACEI/ARB with placebo. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The use of ACEI and/or ARB appears to be safe and to reduce proteinuria in pediatric patients with IgAN. Nonetheless, further randomized controlled trials, with greater methodological rigor and longer follow-up time, are required to establish the efficacy and safety of this therapy in this population. SYSTEMATIC REVIEW REGISTRATION NUMBER: The protocol of this systematic literature review was registered in PROSPERO under the number CRD42021245375, and in the OSF registries ( https://osf.io/qft4z/ ) with the registration https://doi.org/10.17605/OSF.IO/VADYR . A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Antagonistas de Receptores de Angiotensina , Glomerulonefritis por IGA , Adulto , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Niño , Estudios Transversales , Femenino , Glomerulonefritis por IGA/tratamiento farmacológico , Humanos , Masculino , Proteinuria/tratamiento farmacológico , Adulto Joven
11.
J Inherit Metab Dis ; 44(4): 1070-1082, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33443316

RESUMEN

Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analyzed brain MRIs in order to characterize and better understand neuroimaging changes and to re-evaluate the diagnostic role of brain MRI in iMNDs. 81 MRIs of 70 patients (0.1-52.9 years, 39 patients with tetrahydrobiopterin deficiencies, 31 with primary disorders of monoamine metabolism) were retrospectively analyzed and clinical records reviewed. 33/70 patients had MRI changes, most commonly atrophy (n = 24). Eight patients, six with dihydropteridine reductase deficiency (DHPR), had a common pattern of bilateral parieto-occipital and to a lesser extent frontal and/or cerebellar changes in arterial watershed zones. Two patients imaged after acute severe encephalopathy had signs of profound hypoxic-ischemic injury and a combination of deep gray matter and watershed injury (aromatic l-amino acid decarboxylase (AADCD), tyrosine hydroxylase deficiency (THD)). Four patients had myelination delay (AADCD; THD); two had changes characteristic of post-infantile onset neuronal disease (AADCD, monoamine oxidase A deficiency), and nine T2-hyperintensity of central tegmental tracts. iMNDs are associated with MRI patterns consistent with chronic effects of a neuronal disorder and signs of repetitive injury to cerebral and cerebellar watershed areas, in particular in DHPRD. These will be helpful in the (neuroradiological) differential diagnosis of children with unknown disorders and monitoring of iMNDs. We hypothesize that deficiency of catecholamines and/or tetrahydrobiopterin increase the incidence of and the CNS susceptibility to vascular dysfunction.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico por imagen , Errores Innatos del Metabolismo de los Aminoácidos/patología , Encéfalo/patología , Imagen por Resonancia Magnética , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
12.
J Org Chem ; 86(18): 13169-13174, 2021 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-34464119

RESUMEN

Theoretical calculations, associated with control experiments, were carried out to gain insights into the mechanism and origin of enantioselectivity in the phosphoric-acid-catalyzed dynamic kinetic resolution of azlactones. The results revealed a Münchnone intermediate as the key species involved in the isomerization of azlactone rings. The developed model was successfully employed in the comprehension and prediction of enantioselectivity under diverse of reaction conditions, including alcoholysis and aminolysis protocols.


Asunto(s)
Catálisis , Cinética , Estereoisomerismo
13.
Sci Technol Adv Mater ; 21(1): 849-855, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33536838

RESUMEN

Recently, a massive magnetocaloric effect near the liquefaction temperature of hydrogen has been reported in the ferromagnetic material HoB2. Here we investigate the effects of Dy substitution in the magnetocaloric properties of Ho1-x Dy x B2 alloys (x = 0, 0.3, 0.5, 0.7, 1.0). We find that the Curie temperature (T C) gradually increases upon Dy substitution, while the magnitude of the magnetic entropy change |ΔS M| and adiabatic temperature change ΔT ad showed a gradual decrease. On the other hand, due to the presence of successive transitions in these alloys, the peak height of the above magnetocaloric properties tends to be kept in a wide temperature range, leading to a relatively robust figure of merit in a wide temperature span. These alloys could be interesting candidates for magnetic refrigeration in the temperature range of 10-60 K.

14.
Org Biomol Chem ; 18(28): 5420-5426, 2020 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-32696795

RESUMEN

Methylthiolation reactions are usually explored to access organosulfur compounds using methanethiol, an extremely flammable and toxic compound. Herein, methylthiomethyl esters were successfully applied as novel methylthiolation reagents in a low cost, transition-metal-free methodology. These reagents allowed the methylthiolation of a wide scope of chalcones, acyl ester derivatives and Morita-Baylis-Hillman acetates with good group tolerance, affording the methylthiolated products in moderate to excellent yields. The reaction mechanism was investigated through several control experiments, as well as by theoretical calculations employing Density Functional Theory. The results strongly support that a sulfurane and a sulfonium ylide appear as key intermediates and that a Pummerer type rearrangement is also crucial for the formation of this novel reagent. Furthermore, the methylthiolation mechanism is likely to proceed through the nucleophilic attack of the reagent, followed by an entropically favoured step involving the acetate attack to the positively charged species, then releasing the product.

15.
Chemistry ; 25(72): 16555-16563, 2019 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-31647594

RESUMEN

A novel methodology for the 1,1-dichlorocyclopropanation of dicarbonyl conjugated olefins was described. The developed protocol is simple and uses readily accessible starting materials, allowing the isolation of the desired adducts in moderate to excellent yields (up to 99 %). Furthermore, the reaction tolerated scale up to the gram scale; thus highlighting the synthetic potential of this transformation. Control experiments and DFT studies revealed that the reaction proceeded through a Michael-initiated ring-closure process, in which reaction temperature played a crucial role. Finally, these gem-dichlorocyclopropanes were also employed in the preparation of a trisubstituted naphthyl derivative and a diastereoselective reduction was also demonstrated.

16.
J Org Chem ; 84(19): 12573-12582, 2019 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-31524388

RESUMEN

The theoretical-guided evaluation of the Steglich rearrangement of azlactones and isoxazolones allowed the determination of the reactivity patterns in these heterocycles, including the factors that drive the regioselectivity toward both possible sites. These results allowed the first experimental report on the regioselective Steglich rearrangement of isoxazolones, affording the nitrogen- or carbon-acyloxy adducts.

17.
J Org Chem ; 83(24): 15144-15154, 2018 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-30450907

RESUMEN

The first report of the preparation of symmetric and nonsymmetric diaminotruxinic derivatives through the photoredox [2 + 2] cycloadditions of Erlenmeyer azlactones is described, affording the desired compounds in high regio- and diastereocontrol (only head-to-head coupling). Mechanistic studies by DFT suggest that the reaction proceeds through a neutral photocatalytic pathway.

18.
Environ Monit Assess ; 190(9): 560, 2018 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-30159642

RESUMEN

Ozone and a Fe2+/TiO2-based catalyst were examined in the degradation of a synthetic solution of benzene toluene and xylene (BTX) in an advanced oxidation process (AOP). The catalyst beads were made from the slurry waste of aluminum production process, by inserting the TiO2 content and subsequent calcination. The reduction of the BTX concentration load was monitored by the reduction of chemical oxygen demand (COD) and BTX concentration. Different levels were used on factors: pH, time of treatment, initial concentration of BTX, and percentage of TiO2. The process was conducted in a bubble column reactor with the insertion of catalyst beads. A response surface methodology technique (CCD) was used to build a model based on COD reduction results. The model was optimized using the normal-boundary intersection (NBI) algorithm to maximize COD reduction and minimize the variance attributed to the process. Optimization led to COD reductions of 80% in 2 h of experiment. Correlation analysis of coefficient models from experimental data R2adj was 0.9966, showing a good fit of model data. In the optimized conditions, the possible increase of the biodegradability ratio of the BTX solution, through the biochemical oxygen demand (BOD) and COD, was also analyzed. Under pre-treatment conditions, the BOD/COD ratio was 0.13. After the treatment, it increased to 0.56. Graphical abstract ᅟ.


Asunto(s)
Benceno/química , Sedimentos Geológicos/química , Ozono/química , Titanio/química , Tolueno/química , Eliminación de Residuos Líquidos/métodos , Xilenos/química , Algoritmos , Aluminio , Biodegradación Ambiental , Análisis de la Demanda Biológica de Oxígeno , Catálisis , Monitoreo del Ambiente , Peróxido de Hidrógeno/química , Concentración de Iones de Hidrógeno , Industria Manufacturera , Oxidación-Reducción , Soluciones
19.
Biometals ; 30(6): 841-857, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28840394

RESUMEN

Novel lipophilic gold(I) complexes containing 1,3,4-oxadiazol-2-thione or 1,3-thiazolidine-2-thione derivatives were synthesized and characterized by IR, high resolution mass spectrometry, and 1H, 13C 31P NMR. The cytotoxicity of the compounds was evaluated considering cisplatin and/or auranofin as reference in different tumor cell lines: colon cancer (CT26WT), metastatic skin melanoma (B16F10), breast adenocarcinoma (MCF-7), cervical carcinoma (HeLa), glioblastoma (M059 J). Normal human lung fibroblasts (GM07492-A) and kidney normal cell (BHK-21) were also evaluated. The gold(I) complexes were more active than their respective free ligands and cisplatin. Furthermore, antibacterial activity was evaluated against Gram-positive bacteria Staphylococcus aureus ATCC 25213, Staphylococcus epidermidis ATCC 12228 and Gram-negative bacteria Escherichia coli ATCC 11229 and Pseudomonas aeruginosa ATCC 27853 and expressed as the minimum inhibitory concentration (MIC). The complexes exhibited lower MIC values when compared to the ligands and chloramphenicol against Gram-positive bacteria and Gram-negative bacteria. Escherichia coli was sensitive one to the action of gold(I) complexes.


Asunto(s)
Antibacterianos/farmacología , Antineoplásicos/farmacología , Compuestos Orgánicos de Oro/química , Compuestos Orgánicos de Oro/farmacología , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Técnicas de Química Sintética , Cricetinae , Evaluación Preclínica de Medicamentos , Escherichia coli/efectos de los fármacos , Humanos , Espectroscopía de Resonancia Magnética , Ratones , Pruebas de Sensibilidad Microbiana , Compuestos Orgánicos de Oro/síntesis química , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Tionas/química
20.
Biometals ; 30(6): 859, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29022284

RESUMEN

This article has been corrected. One of the author names was given incorrect. Please find in this erratum the correct author name: "Heloiza Diniz Nicolella" that should be regarded as final by the reader.

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