Twelve 7‐chloroquinoline derivatives were designed and synthesized using the principle of molecular hybridization through the coupling of 2‐[2‐(7‐chloroquinolin‐4‐ylthio)‐4‐methylthiazol‐5‐yl]acetic acid 1 with various benzoyl hydrazines 2a–l. The synthetic compounds were tested as antimalarials. Some of them showed an efficient in vitro activity as inhibitors of β‐hematin formation and an in vivo activity in a murine model, resulting in compounds 8 and 9 as the most active ones with IC50 values of 0.65 ± 0.09 and 0.64 ± 0.16 µM, respectively. The effects of the compounds on the cell viability, cell cycle, and apoptosis induction of A549 and MCF‐7 cancer cell lines were also examined. Our data showed that compounds 6 and 12 were the most active agents, decreasing the cell viability of MCF‐7 cells with IC50 values of 15.41 and 12.99 µM, respectively. None of the compounds analyzed significantly affected the viability of peripheral blood mononuclear cells. Also, significant induction of apoptosis was observed when both cancer cell lines were incubated with compounds 6 and 12. In MCF‐7 cells, treatment with these compounds led to cell cycle arrest in the G0/G1 phase. The results obtained suggest that these structures may be useful in developing new therapies for malaria and cancer treatment.
Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients’ immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children’s Hospital (2021–2022). The lymphocyte subpopulations were analyzed by flow cytometry, and IFNγ, IL-6, and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month to 18 years. The majority, 52.8%, had mild disease, and 30.6% of the patients were diagnosed with MIS-C. The main symptoms reported were fever, cough, and diarrhea. A correlation was found between IL-10 and IL-6 concentrations and age group, lymphocyte subpopulations and nutritional status and steroid use, and IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.
La infección por SARS-CoV-2 ha infectado a más de 50 millones de personas con un rango de letalidad de 3 %-10 % de los casos. En Venezuela, cerca de 95 mil casos se han reportado con una letalidad del 1 %. El objetivo de este estudio es evaluar las diferentes poblaciones linfocitarias, analizar los posibles marcadores pronósticos y compararlos con la literatura. Un total de 18 pacientes positivos, por la prueba de transcriptasa reversa más reacción de la cadena de polimerasa (RT-PCR), fueron analizados 12 (5 masculinos) moderados, rango de edad 15-71 años, 6 (4 masculinos) severos (rango de edad 29-50 años) y 100 controles de la misma edad y sexo. Se encontró linfopenia en ambos grupos de pacientes con disminución significativa de linfocitos T. La población de células de memoria al igual que las células CD25 disminuye en la infección viral. Sin embargo, en los pacientes jóvenes del grupo moderado, se observaron los valores más altos de linfocitos T y valores normales de memoria sugiriendo la pronta resolución del proceso infeccioso. En conclusión, los disminución de linfocitos T y células CD25 está relacionada con la infección viral y CD45RO es un marcador de severidad en la población adulta.
Desde el inicio de la pandemia causada por el SARS-CoV-2, se han realizado numerosos estudios sobre métodos diagnósticos específicos, rápidos y económicos que permitieran identificar a los individuos que ha sufrido la infección natural o han sido vacunados. Esto con el objetivo de poder cortar la cadena de transmisión del virus de forma eficiente. Sin embargo, se requieren de controles sanos que no hayan sido expuestos al virus u otros coronavirus para establecer el rango basal de anticuerpos neutralizantes anti-SARS-CoV-2.
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