This study aimed to isolate, purify and characterize secondary metabolites present in Amburana acreana leaves, native to the state of Rondônia, using classical chromatographic methods and 1D, 2D ...nuclear magnetic resonance spectroscopy. From the hydroethanolic leaves extract of A. acreana, p-hydroxybenzoic acid, vanillic acid, coumarin, campesterol 3-β-D-glucoside and amburoside B, all known compounds, were identified. To the best of our knowledge, this is the first report of isolation and chemical characterization of secondary metabolites in A. acreana. In addition, in vitro assays indicated that amburoside B does not have inhibitory potential on the growth of gram-negative bacteria. The presence of these compounds suggests that, thus far, amburosides (A and B) could be chemotaxonomic markers of the genus Amburana.
The present work describes the acetylcholinesterase inhibitory activity of
extracts besides the chemical composition of chromatographic fractions. The hexane, dichloromethane and ethyl acetate ...extract soluble fractions showed high
acetylcholinesterase (
AChE) inhibition (92.18, 71.86 and 74.25%, respectively) while the butanolic and aqueous extracts showed moderate to low activities (44.48 and 20.74%, respectively). The high-performance liquid chromatography coupled with electrospray ionization multiple-stage mass spectrometry (HPLC-ESI-MS
) analysis led to the identification of the alkaloids and flavonol glycoside derivatives present in these extracts. The binding profile of the alkaloids and their atomic effect on 3D structure of
AchE (EelAChE) were assessed with molecular modeling.
This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. ...In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from −6.2 to −9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein–ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.
Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of ...species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA −265.95 ± 1.32 kJ/mol and −124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = −216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= −435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes.
Tetragonisca angustula honey was fractioned in a SiO2 column to furnish three fractions (A–C) in which four hydroxycinnamic acid‐Spermidine amides (HCAAs), known as N′, N″, N‴—tris‐p‐coumaroyl ...spermidine, N′, N″—dicaffeoyl, N‴—coumaroyl spermidine, N′, N″, N‴—tris‐caffeoyl spermidine and N′, N″—dicaffeoyl and N‴—feruloyl spermidine were identified in the fractions B and C by electrospray ionization tandem mass spectrometry. A primary culture model previously infected with Neospora caninum (72 h) was used to evaluate the honey fractions (A–C) for two‐time intervals: 24 and 72 h. Parasitic reduction ranged from 38% on fraction C (12.5 µg/ml), after 24 h, to 54% and 41% with fractions B and C (25 µg/ml) after 72 h of treatment, respectively. Additionally, HCAAs did not show any cell toxicity for 24 and 72 h. For infected cultures (72 h), the active fractions B (12.5 µg/ml) and C (25 µg/ml) decreased their NO content. In silico studies suggest that HCAAs may affect the parasite's redox pathway and improve the oxidative effect of NO released from infected cells. Here, we presented for the first time, that HCAAs from T. angustula honey have the potential to inhibit the growth of N. caninum protozoa.
Tetragonisca angustula honey contain hydroxicinnamic acid – spermidine amides. Hydroxycinnamic acid‐Spermidine amides inhibited the TcTR and PfGR enzymes of the Neospora caninum's redox pathway. The HCAAs reduced the amount of N. caninum tachyzoites in glial cells by up to 54%.
We hypothesized that exercise-related periodic breathing (EPB) would be associated with poor prognosis in advanced chronic heart failure (CHF).
Patients with CHF might present instability of the ...ventilatory control system characterized by cyclic waxing and waning of tidal volume (periodic breathing PB). This condition is associated with several deleterious circulatory and neuro-endocrine responses; in fact, PB in awake and asleep patients has been identified as an independent risk factor for cardiac death. During exercise, however, the prognostic value of PB is still unknown in CHF patients awaiting heart transplantation.
Eighty-four patients with established CHF (65 male, 19 female) were submitted to clinical evaluation, echocardiogram, ventricular scintigraphy, determination of resting serum norepinephrine levels, and an incremental cardiopulmonary exercise test on cycle ergometer. Patients were followed for up to 49.7 months (median = 15.3), and 26 patients (30.9%) died during this period.
Twenty-five of 84 patients presented EPB (29.7%). The following variables were related to mortality according to Kaplan-Meier and univariate Cox regression analysis: EPB (p = 0.004), New York Heart Association class (p = 0.04), serum norepinephrine (p = 0.06), peak oxygen uptake (ml·min−1·kg−1and % predicted; p = 0.085 and p = 0.10, respectively), slope of the ratio of change in minute ventilation to change in carbon dioxide output during exercise (p = 0.10), and scintigraphic left ventricular ejection fraction (p = 0.10). Cox multivariate analysis identified EPB as the only independent variable for cardiac death prediction (p = 0.007). Therefore, EPB alone was associated with a 2.97-fold increase in risk of death in this population (95% confidence interval = 1.34 to 6.54).
Exercise-related periodic breathing independently predicts cardiac mortality in CHF patients considered for heart transplantation.
Mortality is high in patients with acute coronary failure and cardiogenic shock. The most commonly used device for hemodynamic support is the intra-aortic balloon, which, however, may be insufficient ...in patients with refractory cardiogenic shock. This is a case report of a patient complaining of two days of intense and oppressive chest pain, radiating to the left arm. The ECG showed ST elevation. The patient was submitted to angioplasty and stent implant in the anterior descending artery and developed cardiogenic shock refractory to vasoactive drugs and intra-aortic balloon. Hemodynamic measures were carried out and we chose to use an Impella 2.5 device, by percutaneous route, for circulatory support.
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