Synthesis and cytotoxic evaluation of heterocyclic compounds by vinylic substitution of ketene dithioacetals.

N-heterocyclic compounds are important molecular scaffolds in the search for new drugs, since most drugs contain heterocyclic moieties in their molecular structure, and some of these classes of heterocycles are able to provide ligands for two or more biological targets. Ketene dithioacetals are important building blocks in organic synthesis and are widely used in the synthesis of N-heterocyclic compounds. In this work, we used double vinylic substitution reactions on ketene dithioacetals to synthesize a small library of heterocyclic derivatives and evaluated their cytotoxic activity in breast and ovarian cancer cells, identifying two benzoxazoles with good potency and selectivity. In silico predictions indicate that the two most active derivatives exhibit physicochemical properties within the range of drug-like compounds and showed potential to interact with HDAC8 and ERK1 cancer-related targets.

Acetylated galactopyranosyl N-heterocyclic monocarbene complexes of Silver(I) as novel anti-proliferative agents in a rhabdomyosarcoma cell line.

Herein, four silver(I) complexes bearing acetylated d-galactopyranoside-based N-heterocyclic carbene ligands were synthesized and fully characterized by elemental analysis, NMR, and X-ray photoelectron spectroscopy. All complexes were obtained with an anomeric ß-configuration and as monocarbene species. In this study, we investigated the biological effects of the silver(I) complexes 2a-d on the human rhabdomyosarcoma cell line, RD. Our results show concentration-dependent effects on cell density, growth inhibition, and activation of key signaling pathways such as Akt 1/2, ERK 1/2, and p38-MAPK, indicating their potential as anticancer agents. Notably, at 35.5 µM, the complexes induced mitochondrial network disruption, as observed with 2b and 2c, whereas with 2a, this disruption was accompanied by nuclear content release. These results provide insight into the utility of carbohydrate incorporated NHC complexes of silver(I) as new agents in cancer therapy.

Antitumor copper(II) complexes with hydroxyanthraquinones and N,N-heterocyclic ligands.

Five ternary copper(II) complexes, [Cu2(phen)2(L1)(ClO4)2] (1), [Cu2(phen)2(L1)(DMSO)2](PF6)2 (2), [Cu2(bpy)2(L1)(ClO4)2(H2O)2] (3), [Cu2(dmp)2(L1)(ClO4)2(H2O)2] (4), and [Cu(phen)(L2)]2(ClO4)2 (5), in which phen = 1,10-phenanthroline, bpy = 2,2'-bipyridine, dmp = 2,9-dimethyl-1,10-phenanthroline, H2L1 = 1,4-dihydroxyanthracene-9,10-dione and HL2 = 1-hydroxyanthracene-9,10-dione, DMSO = dimethylsulfoxide, were synthesized and fully characterized. Complex 2 was obtained through the substitution of perchlorate for DMSO. When two hydroxyquinone groups are present, L1 makes a bridge between two Cu(II) ions, which also bind two nitrogens of the respective diimine ligand. The compounds bind to calf thymus DNA and oxidatively cleave pUC19 DNA according to the following order of activity 1 > 4-5 > 3. Furthermore, complexes 1, 3, 4 and 5 inhibit topoisomerase-I activity and the growth of myelogenous leukemia cells with the IC50 values of 1.13, 10.60, 0.078, and 1.84 µmol L-1, respectively. Complexes 1 and 4 are the most active in cancer cells and in DNA cleavage.

New europium-doped carbon nanoparticles showing long-lifetime photoluminescence: Synthesis, characterization and application to the determination of tetracycline in waters.

The growing appearance of antibiotic-resistant strains of microorganisms originated from the widespread use and ubiquitous presence of such drugs is a major concern in the world. The development of methodologies able to detect such substances at low concentration in real water samples is mandatory to overcome this problem. Europium(III) is known to form complexes with tetracycline (TC) with photoluminescent characteristics useful for TC determination. In the present work, we synthesized for the first time carbon nanoparticles (CN) showing delayed photoluminescence using a Europium(III) doping synthesis. The new material (PCNEu) was characterized both morphologically and spectroscopically, showing an analytical photoluminescent signal in presence of TC, arising from the 5D0→7F2 transition of europium, one hundred times higher than that of the europium salt alone in presence of the antibiotic. This enhancement is a consequence of the amplifying effect exerted by nanoparticle structure itself, leading to an efficient synergistic "antenna effect" in the system PCNEu - TC. The analytical signal is affected both by pH and the nature of the buffer used, and it allows the detection of tetracycline in waters with a limit of detection of 2.18 nM and recoveries between 90 and 110%. The analytical performance of the developed methodology enables having lower limits of detection than other luminescent and chemiluminescent reported methodologies.

Economic evaluation of plerixafor addition in the mobilization and leukapheresis of hematopoietic stem cells for autologous transplantation: a systematic review.

INTRODUCTION: Although plerixafor in association with granulocyte colony-stimulating factor (G-CSF) can improve mobilization and collection of hematopoietic stem cells (HSC) by leukapheresis, cost may limit its clinical application. The present study systematically reviews economic evaluations of plerixafor plus G-CSF usage compared to G-CSF alone and compares different strategies of plerixafor utilization in multiple myeloma and lymphoma patients eligible for autologous HSC transplantation. AREAS COVERED: Relevant economic evaluations, partial or complete, were searched on PubMed, Embase, LILACS, and Cochrane Central Register of Controlled Trials for a period ending 30 June 2021. This systematic review was reported following the PRISMA Statement. Six economic evaluations were included, considering the use of upfront or just-in-time plerixafor compared to G-CSF alone or other plerixafor strategies. Most comparisons showed both increased cost and health benefits with the addition of plerixafor. Most analyses favored just-in-time plerixafor compared to upfront plerixafor, with a probable preference for broader cutoffs for just-in-time plerixafor initiation. EXPERT OPINION: Plerixafor is a potentially cost-effective technology in the mobilization of HSC in patients with multiple myeloma and lymphomas eligible for autologous HSC transplantation. There is a decreased number of leukapheresis sessions and remobilizations and a higher yield of CD34+ cells.

Isoxazolinas no tratamento da demodicidose canina ­ Revisão de literatura / Isoxazolines in the treatment of canine demodicosis ­ literature review / Isoxazolinas en el tratamiento de la demodicosis canina ­ revisión de la literatura

A demodicidose canina é uma dermatopatia parasitária inflamatória comum na rotina clínica. Ela é causada pela proliferação exacerbada do ácaro Demodex spp., e a espécie mais frequentemente encontrada e que causa a doença clínica é o Demodex canis. A doença pode ser classificada conforme a distribuição das lesões e a idade em que elas surgem. Os sinais clínicos mais comuns incluem alopecia, eritema, hiperpigmentação e descamação, e o diagnóstico mais preconizado é o exame parasitológico do raspado cutâneo. Diversos protocolos terapêuticos para a demodicidose canina têm sido estudados, e por muito tempo utilizou-se o amitraz, sendo ao longo dos anos substituído por fármacos da classe das lactonas macrocíclicas, pela praticidade de sua administração. Contudo, mais recentemente, as isoxazolinas (fluralaner, afoxolaner e sarolaner) foram descobertas como miticidas, e nos últimos anos têm demonstrado excelentes resultados. O presente trabalho tem como objetivo realizar uma revisão de literatura sobre as isoxazolinas no tratamento da demodicidose canina.(AU)

Canine demodicosis is an inflammatory parasitic skin disease common in clinical routine. It is caused by the exacerbated proliferation of the Demodex spp., and the most frequently encountered species that causes clinical disease is Demodex canis. The disease can be classified according to the distribution of lesions and the age at which they appear. The most common clinical signs include alopecia, erythema, hyperpigmentation and desquamation, and the most recommended diagnosis is the parasitological examination of the skin scraping. Several therapeutic protocols for canine demodicosis have been studied, and for a long time the main therapeutic of this disease was amitraz, being replaced over the years by drugs of the macrocyclic lactone class due to the practicality of its administration. However, more recently the isoxazolines (fluralaner, afoxolaner and sarolaner) were discovered as miticides, and in recent years they have shown excellent efficacy results, coming to revolutionize the therapy of canine demodicosis. The present study aims to review the literature on isoxazolines in the treatment of canine demodicosis.(AU)

La demodicosis canina es una enfermedad inflamatoria parasitaria de la piel común en la rutina clínica. Es causada por la proliferación exacerbada de Demodex spp., y la especie más frecuente que causa enfermedad clínica es Demodex canis. La enfermedad se puede clasificar según la distribución de las lesiones y la edad en que aparecen. Los signos clínicos más frecuentes incluyen alopecia, eritema, hiperpigmentación y descamación, y el diagnóstico más recomendado es el examen parasitológico del raspado cutáneo. Se han estudiado varios protocolos terapéuticos para la demodicosis canina, y durante mucho tiempo la principal terapéutica de esta enfermedad fue el amitraz, siendo reemplazada con el paso de los años por fármacos de la clase de las lactonas macrocíclicas debido a la practicidad de su administración. Sin embargo, más recientemente se descubrieron las isoxazolinas (fluralaner, afoxolaner y sarolaner) como acaricidas, y en los últimos años han mostrado excelentes resultados de eficacia, llegando a revolucionar la terapia de la demodicosis canina. El presente estudio tiene como objetivo revisar la literatura sobre las isoxazolinas en el tratamiento de la demodicosis canina.(AU)

Steric and Electronic Effects in N-Heterocyclic Carbene Gold(III) Complexes: An Experimental and Computational Study.

A series of neutral acridine-based gold(III)-NHC complexes containing the pentafluorophenyl (-C6F5) group were synthesized. All of the complexes were fully characterized by analytical techniques. The square planar geometry around the gold center was confirmed by X-ray diffraction analysis for complexes 1 (Trichloro [1-methyl-3-(9-acridine)imidazol-2-ylidene]gold(III)) and 2 (Chloro-bis(pentafluorophenyl)[1-methyl-3-(9-acridine)imidazol-2-ylidene]gold(III)). In both cases, the acridine rings play a key role in the crystal packing of the solid structures by mean of π-π stacking interactions, with centroid-centroid and interplanar distances being similar to those found in other previously reported acridine-based Au(I)-NHC complexes. A different reactivity when using a bulkier N-heterocyclic carbene ligand such as 1,3-bis-(2,6-diisopropylphenyl)-2-imidazolidinylidene (SIPr) was observed. While the use of the acridine-based NHC ligand led to the expected organometallic gold(III) species, the steric hindrance of the bulky SIPr ligand led to the formation of the corresponding imidazolinium cation stabilized by the tetrakis(pentafluorophenyl)aurate(III) [Au(C6F5)4]- anion. Computational experiments were carried out in order to figure out the ground state electronic structure and the binding formation energy of the complexes and, therefore, to explain the observed reactivity.

Colchicina, perspectivas de un viejo amigo para la reumatología en la COVID-19: una revisión exploratoria / no

Introducción: La colchicina es ampliamente utilizada en enfermedades inflamatorias como la gota y la fiebre mediterránea familiar. Debido a su capacidad inmunomoduladora, podría tener un papel importante en el tratamiento de la COVID-19. Objetivo: Explorar la evidencia médica publicada hasta el 28 de diciembre del 2020, acerca de la eficacia y la seguridad de la colchicina en el tratamiento de pacientes con infección confirmada por SARS-CoV-2. Material y métodos: Revisión exploratoria de la literatura que incluyó PubMed y Scopus. Se tuvieron en cuenta registros de ensayos clínicos y publicaciones con datos empíricos (estudios observacionales y experimentales) en inglés y español. Resultados: Se encontraron 33 ensayos clínicos y 6 publicaciones empíricas: estudios de cohorte prospectivos (n = 2) y retrospectiva (n = 2), ensayo clínico aleatorizado (n = 1) y estudio casos y controles (n = 1). La suma de los participantes en los ensayos es de 46.324 individuos, el 73% (24/33) de los estudios recluta a la población de estudio y el 51% (17/33) son fase 3. Conclusiones: Un ensayo clínico respalda la disminución en marcadores inflamatorios pronósticos y el tiempo de estancia hospitalaria en la infección por SARS-CoV-2. Los ensayos clínicos en desarrollo ayudarán a esclarecer la eficacia y la seguridad de la colchicina para el manejo de pacientes con COVID-19.

Introduction: Colchicine is widely used to treat inflammatory diseases such as gout and Mediterranean fever. Due to its immunomodulatory capacity, it could play an important role in the treatment of COVID-19. Objective: To explore the current available medical evidence, published until 28 December 2020, regarding the efficacy and safety of colchicine in the treatment of patients with confirmed SARS-CoV-2 infection. Material and methods: Scoping review of the literature that included PubMed and Scopus. Records of clinical trials and publications with empirical data (observational and experimental studies) in English and Spanish were included. Results: A total of 33 clinical trials and 6 publications were found: prospective (n = 2) and retrospective (n = 2) cohort studies, randomised clinical trials (n = 1) and case-control studies (n = 1). The total number of participants in the trials is 46,324 individuals, 73% (24/33) of the studies are recruiting participants and 51% (17/33) are phase 3 studies. Conclusions: One clinical trial reports a decrease in prognostic inflammatory markers and length of hospital stay in SARS-CoV-2 infection. The ongoing clinical trials will clarify the efficacy and safety of colchicine for the management of patients with COVID-19.

Systemic lupus erythematosus: Pharmacological differences between women and men and among age groups and geographical regions

Systemic lupus erythematosus (SLE) is a chronic and potentially fatal autoimmune disease. There are clinical differences between women and men and among age groups. Its treatment involves a heterogeneous group of drugs. The objective was to determine the pharmacological treatment patterns in a group of patients with SLE and compare them according to sex, age group and geographic region. This was a cross-sectional study that identified outpatient drugs used in patients with SLE from a population database of Colombians affiliated with the Colombian Health System. Sociodemographic and pharmacological variables were considered. Descriptive and bivariate analyses were performed. A total of 4307 patients with SLE were identified (median age, 44.2 years; 89.4% women). Disease-modifying antirheumatics were the most prescribed drugs (90.5%), especially chloroquine (54.4%), which predominated in all age groups and geographical regions. Hydroxychloroquine and methotrexate were the predominant prescribed drugs for women, while corticosteroids, chloroquine, azathioprine, and mycophenolate were the predominant prescribed drugs for men. The use of corticosteroids (prednisolone and prednisone) decreased with increasing age. Differences were found in the prescription of drugs for patients with SLE between women and men and among geographic regions and age groups. The use of chloroquine predominated over hydroxychloroquine, contrasting with clinical practice guidelines.

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune crónica y potencialmente mortal. Existen diferencias clínicas entre mujeres y hombres, y entre grupos de edad. Su tratamiento involucra un grupo heterogeneo de medicamentos. El objetivo fue determinar los patrones de tratamiento farmacológico de un grupo de pacientes con LES y compararlos según el sexo, los grupos de edad y las regiones geograficas. Estudio de corte transversal que identifico los medicamentos de uso ambulatorio empleados en pacientes con LES, a partir de una base de datos poblacional de colombianos afiliados al Sistema de Salud de Colombia. Se consideraron variables sociodemográficas y farmacologicas. Se realizo un análisis descriptivo y bivariado. Se identificó a 4.307 pacientes con LES, con una mediana de edad 44,2 an˜ os y un 89,4% mujeres. Los medicamentos modificadores de enfermedad reumatica fueron los mas prescritos (90,5%), en especial cloroquina (54,4%), el cual predomino en todos los grupos de edad y las regiones geográficas. La hidroxicloroquina y el metotrexato predominaron en mujeres, mientras que los corticosteroides, la cloroquina, la azatioprina y el micofenolato, en hombres. Con el aumento de la edad disminuyo el uso de corticoides (prednisolona y prednisona). Se encontraron diferencias en la prescripción de los medicamentos empleados en los pacientes con LES entre mujeres y hombres, regiones geográficas y grupos etarios. El uso de cloroquina predomino sobre la hidroxicloroquina, en contraste con lo recomendado por las guías de practica clínica.

Mobilized and apheresis-collected endothelial progenitor cells with plerixafor.

BACKGROUND: Endothelial progenitor cells (EPCs) are immature cells able to proliferate and contribute to endothelial repair, vascular homeostasis, neovascularization, and angiogenesis. It therefore seems likely that circulating EPCs have therapeutic potential in ischemic and vascular diseases. In this study we evaluated the efficiency of EPC mobilization and collection by large volume leukapheresis in subjects with hematological diseases, treated with plerixafor in association with G-CSF. METHODS: Twenty-two patients with lymphoid malignancies underwent rHuG-CSF and plerixafor treatment followed by leukapheresis. Blood samples before and after treatment and apheresis liquid sample were taken and analyzed by flow cytometry in order to quantified EPC. RESULTS: The percentage of CD34+ cells and EPCs among circulating total nuclear cells (TNCs) increased significantly by approximately 2-fold and 3-fold, respectively, after plerixafor treatment. Consequently, the absolute number of CD34+ cells and EPCs were increased 4-fold after plerixafor treatment. The median PB concentration of EPCs before and after treatment were 0.77/µL (0.31-2.15) and 3.41/µL (1.78-4.54), respectively, P < .0001. The total EPCs collected per patient were 3.3×107 (0.8×107 -6.8×107 ). CONCLUSION: We have shown that plerixafor in combination with G-CSF allows the mobilization and collection of large amounts of EPCs along with CD34+ cells in lymphoid neoplasm patients. The possibility to collect and to store these cells could represent a promising therapeutic tool for the treatment of ischemic complications without the need of in vitro expansion.

Verificación y transferencia de intervalos de referencia de variables bioquímicas de rutina / Verification and transfer of reference intervals of routine biochemical variables

Introducción. El correcto análisis en la interpretación de los resultados de cualquier analito biológico es esencial para la salud del paciente y está fuertemente ligado a contrastar dichos resultados con los intervalos biológicos referenciales que estén acorde a la población que está siendo analizada diariamente. El objetivo de este artículo, fue establecer intervalos referenciales (IR) en adultos para glicemia, urea, creatinina, ácido úrico, colesterol total y triglicéridos en un laboratorio clínico y comparar los valores obtenidos con los incluidos en los insertos para ese rango de edad. Metodología. La población fue de 561 adultos de ambos sexos, aparentemente sanos, que acudieron a Biomasterclin Laboratorio en Valencia, Venezuela, y cuyas edades fueron de 57,1±18,1 años. Resultados. Los IR obtenidos fueron glicemia 63,0-108,8 mg/dL, urea 17,7-54,9 mg/dL, creatinina 0,60-1,41 mg/dL, ácido úrico 0,89-7,26 mg/dL, colesterol total 78,5-251,1 mg/dL y triglicéridos 39,5-176,0 mg/dL. Los IR propuestos por la casa comercial empleada para la determinación de la glicemia y la creatinina pudieron ser transferidos a la población evaluada, mientras que el resto de los IR no. Conclusión. Debido a las diferencias que se presentan entre los IR en los estuches comerciales comparados con los de la población de individuos que acuden a los laboratorios clínicos, se hace necesario establecer IR para ser empleados en cada laboratorio clínico

The correct analysis in the interpretation of the results of any biological analyte is essential for the health of the patient and it is strongly linked to comparing those results with reference ranges that are in accordance with the population that is being analyzed on a daily basis. The objective of this study was to establish reference ranges in adults for glycemia, urea, creatinine, uric acid, total cholesterol and triglycerides in a clinical laboratory and compare the values obtained with those included in the inserts for the corresponding age group. Methodology. The population consisted of 561 apparently healthy adults of both sexes that attended Biomasterclin Laboratorio in Valencia, Venezuela, whose ages were 57.1±18.1 years. Results. The reference ranges obtained for glycemia were 63.0- 108.8 mg/dL, urea 17.7-54.9 mg/dL, creatinine 0.60-1.41 mg/dL, uric acid 0.89- 726 mg/dL, total cholesterol 78.5-251.1 mg/dL and triglycerides 39.5-176.0 mg/ dL. The reference ranges proposed by the commercial kits used for the determination of glycemia and creatinine could be transferred to the evaluated population, while the rest of the reference ranges could not. Conclusion. Due to the differences that occur between the reference ranges in commercial kits compared to those of the population of individuals who attend clinical laboratories, it is necessary to establish reference values in each clinical laboratory

Design, Synthesis, and in†vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block.

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2-5.4 µM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.

Design, Synthesis, and Characterization of Novel sn-1 Heterocyclic DAG-Lactones as PKC Activators.

DAG-lactones represent useful templates for the design of potent and selective C1 domain ligands for PKC isozymes. The ester moiety at the sn-1 position, a common feature in this template, is relevant for C1 domain interactions, but it represents a labile group susceptible to endogenous esterases. An interesting challenge involves replacing the ester group of these ligands while still maintaining biological activity. Here, we present the synthesis and functional characterization of novel diacylglycerol-lactones containing heterocyclic ring substituents at the sn-1 position. Our results showed that the new compound 10B12, a DAG-lactone with an isoxazole ring, binds PKCα and PKCε with nanomolar affinity. Remarkably, 10B12 displays preferential selectivity for PKCε translocation in cells and induces a PKCε-dependent reorganization of the actin cytoskeleton into peripheral ruffles in lung cancer cells. We conclude that introducing a stable isoxazole ring as an ester surrogate in DAG-lactones emerges as a novel structural approach to achieve PKC isozyme selectivity.

Rabdomiólisis inducida por consumo crónico de bebidas energizantes asociado a ejercicio físico de baja intensidad: reporte de caso / Rhabdomyolysis induced by long-term consumption of energy drinks associated with low intensity physical exercise: case report

RESUMEN Introducción: Un riesgo potencialmente mortal es el hábito de consumo de bebidas energizantes, porque puede producir un síndrome caracterizado por la necrosis muscular que promueve la liberación de enzimas y mioglobina proveniente del interior del miocito hacia la circulación, creando una peroxidación lipídica llegando a generar lesión renal aguda e hyperkalemia; conocido como rabdomiólisis. La rabdomiólisis la esperaríamos encontrar entre 24 y 48 h después de actividades extenuantes, aún más con un índice de Borg modificado mayor o igual a 5 puntos; sin embargo, las bebidas energizantes por su alto contenido de cafeína y otros componentes pueden generar este evento adverso poco conocido. Caso clínico: Paciente de 37 arios, obeso, que ingresó al servicio de urgencias por cuadro clínico de mialgia y orina oscura que apareció 24h después de 4 días de ejercicio muscular de baja intensidad, asociado a consumo diario de bebida energizante por 2 años. El diagnóstico de rabdomiólisis se confirmó por hiperCKemia e hipertrasaminemia; no fue posible medir los niveles de mioglobina. El paciente fue tratado con fluidoterapia agresiva. Nunca presentó complicaciones renales ni hidroelectrolíticas. Conclusión: Nuestro caso destaca la aparición de rabdomiólisis aguda en pacientes sometidos a ejercicios de baja intensidad no descartando como causa principal el consumo crónico de bebidas energizantes. Son pocos casos actualmente reportados en la literatura. Gracias al tratamiento oportuno se evitó la progresión a lesión renal aguda.

ABSTRACT Introduction: The habit of consuming energy drinks is a life-threatening risk, because it can produce a syndrome characterised by a muscle necrosis. This promotes the release of enzy mes and myoglobin from inside the myocyte into the circulation, creating lipid peroxidation and leading to acute kidney injury, and hyperCKemia, together producing rhabdomyolysis. Rhabdomyolysis can be expected to be found within 24 to 48 h after strenuous activities, even more so with a modified Borg index greater than or equal to 5 points. However, energy drinks, due to their high content of caffeine and other components, can generate this little known adverse event. Clinical case: A 37-year-old patient admitted to the emergency department due to clinical symptoms of myalgia, and dark urine that appeared 24 h after four days of low-intensity muscular exercises, and was associated with daily consumption of an energizing drink for 2 years. The diagnosis of rhabdomyolysis was confirmed by increased creatine kinase and transaminases. It was not possible to measure myoglobin levels. The patient was treated with aggressive fluid therapy. He never presented with any renal or electrolyte complica tions. Conclusion: This case highlights the appearance of acute rhabdomyolysis in patients taking low intensity exercises, and not ruling out long-term consumption of energy drinks as the main cause. There are few cases currently reported in the literature. Owing to the timely treatment, progression to acute kidney injury was avoided.

Pharmaceuticals agents for preventing NSAID-induced gastric ulcers: a patent review.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs widely used due to their pharmacological potential, demonstrating anti-inflammatory, analgesic, or antipyretic activity. However, prolonged use of these medications can lead to the development of gastric ulcers in patients. This review aimed to find patents for drugs with an anti-inflammatory and gastroprotective character to treat NSAID-induced gastric ulcers. AREAS COVERED: For the treatment of NSAID-induced gastric ulcers, formulations with different action mechanisms were found, including donors of nitric oxide, heterocyclic compounds, and natural products. EXPERT OPINION: Many of the structures found have already been used in clinic settings and others, and according to the results found, they are promising for the treatment of gastric ulcers.

Effects of seasoning on the formation of heterocyclic amines and polycyclic aromatic hydrocarbons in meats: A meta-analysis.

Cooking improves digestibility, palatability, and microbiological profile of meats, but can produce compounds with carcinogenic potential, such as heterocyclic amines (HAs) and polycyclic aromatic hydrocarbons (PAHs). It has been shown that the formation of these compounds in meats can be inhibited by spiced marinades, but there is a complexity to check and compare the results of isolated studies with so many variables involved. Thus, this work aimed to review studies that evaluated the effects of spices on the formation of HAs and PAHs in meats according to cooking techniques and spice type. A meta-analysis with a random effect model was conducted using response ratios (R) to identify and summarize previous results and answer the research question. The use of spices before frying (R* = 0.52), grilling (R* = 0.63), or roasting (R* = 0.74) meat, and spicing with garlic and onion (R* = 0.57), pepper (R* = 0.63), and other spices with phenolic compounds (R* = 0.63), decrease the formation of HAs and PAHs, due to the antioxidant and electron transfer capacity. In this article, we discuss how the improvement of culinary techniques with the dissemination of knowledge about meat preparation conditions is an effective strategy for reducing the formation and ingestion of HAs and PAHs; this is important due to the growing evidence about the association between meat consumption and chronic diseases. This is the first systematic review with meta-analysis about this topic and can guide industry, food services, and population to improve the safety associated with meat consumption.

On-resin multicomponent protocols for biopolymer assembly and derivatization.

Solid-phase synthesis represents the methodological showcase for technological advances such as split-and-pool combinatorial chemistry and the automated synthesis of peptides, nucleic acids and polysaccharides. These strategies involve iterative coupling cycles that do not generate functional diversity besides that incorporated by the amino acids, nucleosides and monosaccharide building blocks. In sharp contrast, multicomponent reactions (MCRs) are traditionally used to generate both skeletal and appendage diversity in short, batchwise procedures. On-resin MCRs have traditionally been employed for the construction of heterocycle and peptidomimetic libraries, but that scenario has changed recently, and today the focus is more on the solid-phase derivatization of peptides and oligonucleotides. This review presents relevant experimental details and addresses the synthetic scope of such on-resin multicomponent protocols employed to accomplish specific biopolymer covalent modifications that are practically inviable by traditional solution-phase methodologies. Recommendations are provided to facilitate the implementation of solid-supported protocols and avoid possible pitfalls associated with the selection of the polymeric resin, the solvent and the order and amount of the reagents employed. We describe procedures comprising the multicomponent lipidation, biotinylation and labeling of both termini and the side chains, as well as the use of MCRs in the traceless on-resin synthesis of ligated and cyclic peptides. Solid-phase protocols for the assembly of α-helical and parallel ß-sheet peptides as well as hybrid peptide-peptoid and peptide-peptide nucleic acid architectures are described. Finally, the solid-supported multicomponent derivatization of DNA oligonucleotides is illustrated as part of the DNA-encoded library technology relying on MCR-derived heterocyclic compounds.

Fluorinated-NHC Transition Metal Complexes: Leading Characters as Potential Anticancer Metallodrugs.

In the last 20 years, N-Heterocyclic Carbene (NHC) ligands have been ubiquitous in biological and medicinal chemistry. Part of their success lies in the tremendous number of topologies that can be synthesized and thus finely tuned that have been described so far. This is particularly true in the case of those derivatives, including fluorine or fluorinated fragments on their NHC moieties, gaining much attention due to their enhanced biological properties and turning them into excellent candidates for the development of novel metallodrugs. Thus, this review summarizes the development that fluorinated-NHC transition metal complexes have had and their impact on cancer treatment.

Dihydroquinoline derivative as a potential anticancer agent: synthesis, crystal structure, and molecular modeling studies.

Cancer is one of the leading causes of death worldwide and requires intense and growing research investments from the public and private sectors. This is expected to lead to the development of new medicines. A determining factor in this process is the structural understanding of molecules with potential anticancer properties. Since the major compounds used in cancer therapies fail to encompass every spectrum of this disease, there is a clear need to research new molecules for this purpose. As it follows, we have studied the class of quinolinones that seem effective for such therapy. This paper describes the structural elucidation of a novel dihydroquinoline by single-crystal X-ray diffraction and spectroscopy characterization. Topology studies were carried through Hirshfeld surfaces analysis and molecular electrostatic potential map; electronic stability was evaluated from the calculated energy of frontier molecular orbitals. Additionally, in silico studies by molecular docking indicated that this dihydroquinoline could act as an anticancer agent due to their higher binding affinity with human aldehyde dehydrogenase 1A1 (ALDH 1A1). Tests in vitro were performed for VERO (normal human skin keratinocytes), B16F10 (mouse melanoma), and MDA-MB-231 (metastatic breast adenocarcinoma), and the results certified that compound as a potential anticancer agent. A Dihydroquinoline derivative was tested against three cancer cell lines and the results attest that compound as potential anticancer agent.