Design, synthesis, and molecular modeling studies of novel 2-quinolone-1,2,3-triazole-α-aminophosphonates hybrids as dual antiviral and antibacterial agents.

With the aim to identify new antiviral agents with antibacterial properties, a series of 2-quinolone-1,2,3-triazole derivatives bearing α-aminophosphonates was synthesized and characterized by 1H NMR, 13C NMR, 31P NMR, single crystal XRD and HRMS analyses. These compounds were examined against five RNA viruses (YFV, ZIKV, CHIKV, EV71 and HRV) from three distinct families (Picornaviridae, Togaviridae and Flaviviridae) and four bacterial strains (S. aureus, E. feacalis, E. coli and P. aeruginosa). The α-aminophosphonates 4f, 4i, 4j, 4k, 4p and 4q recorded low IC50 values of 6.8-10.91 µM, along with elevated selectivity indices ranging from 2 to more than 3, particularly against YFV, CHIKV and HRV-B14. Besides, the synthesized compounds were generally more sensitive toward Gram-positive bacteria, with the majority of them displaying significant potency against E. feacalis. Specifically, an excellent anti-enterococcus activity was obtained by compound 4q with MIC and MBC values of 0.03 µmol/mL, which were 8.7 and 10 times greater than those of the reference drugs ampicillin and rifampicin, respectively. Also, compounds 4f, 4p and 4q showed potent anti-staphylococcal activity with MIC values varying between 0.11 and 0.13 µmol/mL, compared to 0.27 µmol/mL for ampicillin. The results from DFT and molecular docking simulations were in agreement with the biological assays, proving the binding capability of hybrids 4f, 4i, 4j, 4k, 4p and 4q with viral and bacterial target enzymes through hydrogen bonds and other non-covalent interactions. The in silico ADME/Tox prediction revealed that these molecules possess moderate to good drug-likeness and pharmacokinetic properties, with a minimal chance of causing liver toxicity or carcinogenic effects.

Safety Profile, In Vitro Anti-Inflammatory Activity, and In Vivo Antiulcerogenic Potential of Root Barks from Annona senegalensis Pers. (Annonaceae).

Annona senegalensis (Annonaceae) is a tropical shrub widely distributed in Burkina Faso. This plant is traditionally used as a medicine against many pathologies including typhoid fever, gastrointestinal disorders, ulcers, and inflammatory and infectious diseases. The present study was conducted to evaluate the anti-inflammatory and antiulcer properties of Annona senegalensis root bark extracts. Therefore, toxicity tests were first performed, followed by other biological tests. For this purpose, we first undertook to evaluate the toxicity tests before considering the other biological tests in a second step. The results showed that the extracted fractions had a significant effect for the different methods used (protein denaturation inhibition activity, hyaluronidase inhibition activity, and xanthine oxidase inhibition activity). However, of the extracted fractions used, the ethyl acetate fraction was the most anti-inflammatory fraction. The antiulcer activity was evaluated using the best bioactive fraction. The antiulcer effect of the ethyl acetate fraction may be due to both the reduction of gastric acid secretion and gastric cytoprotection. The results of this study also showed that the bioactive fraction reduced ethanol-induced ulceration and pyloric ligation in a dose-dependent manner, and at the highest dose (200 mg/kg), the effect was similar to that of the reference drug. In summary, the ethyl acetate fraction was found to have the best anti-inflammatory and antiulcerogenic activities. The ethyl acetate fraction at a dose of 200 mg/kg also showed a rather interesting level of cytoprotection. The anti-inflammatory and antiulcer activities could be due to the different secondary metabolites contained in the fractions extracted from Annona senegalensis, notably flavonoids, triterpenoids, steroids, saponins, and tannins. As the mechanisms of action are still little or not understood, we will consider in the future identifying the phytoconstituents and the mechanisms of action involved in the results.

Effects of virgin olive oil phenolic compounds on LDL oxidation and vasorelaxation activity.

This study examined the efficacy of virgin olive oil phenolic extract and other phenolic compounds (oleuropein, caffeic acid) in preventing oxidative modifications of human low density lipoprotein oxidised by CuCl2. The vasorelaxant effect of these compounds on rat aortic ring with and without functional endothelium is also discussed. Olive oil phenolic extract, caffeic acid and oleuropein increased the lag time of conjugated diene formation in a concentration-dependent manner. Moreover, phenolic extract produced a vasorelaxant effect that persisted in denuded aorta and after inhibition of nitric oxide synthase by NG-methyl-L-arginine (L-NMMA) or methylene blue. Oleuropein did not produce a relaxant effect, whereas caffeic acid produced partial relaxation at concentration 0.5 g/L.

[Effect of phenolic compounds of virgin olive oil on LDL oxidation resistance]. / Efecto de los compuestos fenólicos del aceite de oliva virgen sobre la resistencia de las lipoproteínas de baja densidad a la oxidación.

BACKGROUND AND OBJECTIVE: Several epidemiological and experimental studies have associated the intake of antioxidants, which are abundant in the Mediterranean diet, with a low incidence of cardiovascular disease. One possible mechanism of this action is the oxidative protection in low density lipoproteins (LDL). The aim of our study was to compare the antioxidative activity of diverse phenolic compounds present in virgin olive oil on these lipoproteins. SUBJECTS AND METHOD: LDL was isolated from blood plasma of healthy volunteers by sequential ultracentrifugation. This was followed by oxidation with CuC12 in the presence of different concentrations of phenolic compounds and virgin olive oil extract. Production of conjugated dienes was determined by the continuous monitoring of increased absorbency at 234 nm as an indicator of LDL oxidation. RESULTS: Virgin olive oil extract prolonged the latency phase and significantly lowered the progression rate (p < 0.05) at low concentrations (2 g/ml). This antioxidative effect was also observed with low concentrations (2 M) of caffeic acid and oleuropein (p < 0.05). However, it was necessary to increase the concentration of flavone up to 50 times to observe a similar effect (p < 0.05). CONCLUSION: Both virgin olive oil extract enriched in phenolic compounds and phenolic compounds present in olive oil (caffeic acid and oleuropein) are potent antioxidants at very low concentrations. Thus, the beneficial effects of a Mediterranean diet may be partly due to the protective action of these compounds.

Efecto de los compuestos fenólicos del aceite de oliva virgen sobre la resistencia de las lipoproteínas de baja densidad a la oxidación / Effect of phenolic compounds of virgin olive oil on LDL oxidation resistance

FUNDAMENTO Y OBJETIVO: Varios estudios epidemiológicos y experimentales han relacionado la ingestión de antioxidantes, abundantes en la alimentación mediterránea, con una baja incidencia de enfermedad cardiovascular. Uno de los posibles mecanismos de dicha acción es la protección frente a la oxidación de las lipoproteínas de baja densidad (LDL). El objetivo de nuestro estudio fue comparar la actividad antioxidante de diversos compuestos fenólicos, presentes en el aceite de oliva virgen, sobre dichas lipoproteínas. SUJETOS Y MÉTODO: Las LDL fueron aisladas de voluntarios sanos por medio de ultracentrifugación secuencial a partir de plasma sanguíneo. Seguidamente fueron oxidadas con CuCl2 en presencia de diferentes concentraciones de los compuestos fenólicos y de un extracto de aceite de oliva virgen. Se determinó la producción de dienos conjugados, mediante la monitorización continua del aumento de absorción a 234 nm, como indicador de la oxidación de las LDL. RESULTADOS: Los resultados ponen de manifiesto que el extracto de aceite de oliva virgen prolonga la fase de latencia y disminuye la tasa de progresión de manera significativa (p < 0,05) a bajas concentraciones (2 µg/ml). Este efecto antioxidante también se observó con bajas concentraciones (2 µM) de ácido cafeico y oleuropeína (p < 0,05). Sin embargo, fue necesario aumentar 50 veces la concentración de flavona para obtener un efecto similar (p < 0,05). CONCLUSIONES: El extracto de aceite de oliva virgen rico en compuestos fenólicos, así como los compuestos fenólicos presentes en él (ácido cafeico y oleuropeína) son potentes antioxidantes a muy bajas concentraciones. Por tanto, el efecto beneficioso de la alimentación mediterránea puede deberse, en parte, a la acción protectora de dichos compuestos (AU)