Synthesis, Spectroscopic Characterization, Cytotoxic Activity and Molecular Docking Studies of novel series of quinoxaline-2,3-dione Derivatives

Ce travail explore la synthèse de nouveaux dérivés basés sur l'échafaudage quinoxaline-2,3-dione pour développer un nouveau dérivé de quinoxaline biologiquement actif. Ces dérivés ont ensuite été caractérisés à l'aide de techniques spectroscopiques, notamment la RMN du ¹H, la RMN du ¹³C et la spectrométrie de masse. De plus, les propriétés cytotoxiques de chaque composé nouvellement synthétisé ont été évaluées par rapport à trois types distincts de cellules cancéreuses humaines : les cellules cancéreuses du poumon A549, les cellules cancéreuses du col de l'utérus HeLa et les fibroblastes HFF du prépuce humain. L'enquête impliquant ces cellules a révélé un impact substantiel de la durée d'exposition et de la concentration chimique sur la viabilité cellulaire. Parmi les composés testés, le composé 3b présentait la valeur IC50 la plus favorable (29,4 µM). Cela souligne son potentiel en tant que candidat principal pour une exploration plus approfondie dans la poursuite d’interventions thérapeutiques efficaces. Pour démêler les interactions moléculaires anticipées, une approche complète d’amarrage moléculaire a été utilisée. Les composés ont été systématiquement ancrés dans les sites de liaison des protéines 6G77 (associées au cancer du poumon), 1M17 (liées aux cellules Hela) et 1Z68 (liées aux cellules fibroblastiques du prépuce humain). Il est encourageant de constater que les résultats de ces études d’amarrage moléculaire se sont révélés très prometteurs. Les informations recueillies à partir des données recèlent un potentiel pour le développement d’agents antimicrobiens plus puissants

Silver nanoparticles as a potential treatment against SARS‐CoV‐2: A review

[eng] Several human coronaviruses (HCoVs) are distinguished by the ability to generate epidemics or pandemics, with their corresponding diseases characterized by severe respiratory illness, such as that which occurs in severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and, today, in SARS-CoV-2, an outbreak that has struck explosively and uncontrollably beginning in December 2019 and has claimed the lives of more than 1.9 M people worldwide as of January 2021. The development of vaccines has taken one year, which is why it is necessary to investigate whether some already-existing alternatives that have been successfully developed in recent years can mitigate the pandemic's advance. Silver nanoparticles (AgNPs) have proved effective in antiviral action. Thus, in this review, several in vitro and in vivo studies of the effect of AgNPs on viruses that cause respiratory diseases are analyzed and discussed to promote an understanding of the possible interaction of AgNPs with SARS-CoV-2. The study focuses on several in vivo toxicological studies of AgNPs and a dose extrapolation to humans to determine the chief avenue of exposure. It can be concluded that the use of AgNPs as a possible treatment for SARS-CoV-2 could be viable, based on comparing the virus' behavior to that of similar viruses in in vivo studies, and that the suggested route of administration in terms of least degree of adverse effects is inhalation. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

Left ventricular remodeling with exercise in hypertension

We investigated how exercise training superimposed on chronic hypertension impacted left ventricular remodeling. Cardiomyocyte hypertrophy, apoptosis, and proliferation in hearts from female spontaneously hypertensive rats (SHRs) were examined. Four-month-old SHR animals were placed into a sedentary group (SHR-SED; n = 18) or a treadmill running group (SHR-TRD, 20 m/min, 1 h/day, 5 days/wk, 12 wk; n = 18). Age-matched, sedentary Wistar Kyoto (WKY) rats were controls (n = 18). Heart weight was greater in SHR-TRD vs. both WKY (P < 0.01) and SHR-SED (P < 0.05). Morphometric-derived left ventricular anterior, posterior, and septal wall thickness were increased in SHR-SED relative to WKY and augmented in SHR-TRD. Cardiomyocyte surface area, length, and width were increased in SHR-SED relative to WKY and further increased in SHR-TRD. Calcineurin abundance was increased in SHR-SED vs. WKY (P < 0.001) and attenuated in SHR-TRD relative to SHR-SED (P < 0.05). Protein abundance and mRNA of Akt was not different among groups. The rate of apoptosis was increased in SHR-SED relative to WKY and mitigated in SHR-TRD. The abundance of Ki-67+ cells across groups was not statistically different across groups. The abundance of cardiac progenitor cells (c-Kit+ cells) was increased in SHR-TRD relative to WKY. These data suggest that exercise training superimposed on hypertension augmented cardiomyocyte hypertrophy, despite attenuating calcineurin abundance. Exercise training also mitigated apoptosis in hypertension and showed a tendency to enhance the abundance of cardiac progenitor cells, resulting in a more favorable cardiomyocyte number in the exercise-trained hypertensive heart

Intracardiac intracellular angiotensin system in diabetes.

Item does not contain fulltextThe renin-angiotensin system (RAS) has mainly been categorized as a circulating and a local tissue RAS. A new component of the local system, known as the intracellular RAS, has recently been described. The intracellular RAS is defined as synthesis and action of ANG II intracellularly. This RAS appears to differ from the circulating and the local RAS, in terms of components and the mechanism of action. These differences may alter treatment strategies that target the RAS in several pathological conditions. Recent work from our laboratory has demonstrated significant upregulation of the cardiac, intracellular RAS in diabetes, which is associated with cardiac dysfunction. Here, we have reviewed evidence supporting an intracellular RAS in different cell types, ANG II's actions in cardiac cells, and its mechanism of action, focusing on the intracellular cardiac RAS in diabetes. We have discussed the significance of an intracellular RAS in cardiac pathophysiology and implications for potential therapies