Biological activities of Solanum paludosum Moric. extracts obtained by maceration and supercritical fluid extraction

Solanum paludosum extracts obtained by maceration (SP-EtOH_CRUDE and SP-EtOH_MARC) and supercritical fluid extraction (SP-SFECO₂) were evaluated. Three extracts with distinct chromatographic profiles were obtained: SP-EtOH_CRUDE, with a complex phenolic composition; SP-SFECO₂, containing methoxylated flavonoids; and SP-EtOH_MARC, which bears mainly polar polyphenols. All extracts were strong antioxidants, as measured using the diphenylpicrylhydrazyl (DPPH) method, xanthine/xanthine oxidase/luminol and iron-induced lipid peroxidation systems. Extracts were also evaluated as modifiers of antibiotic activity in strains of Staphylococcus aureus expressing fluoroquinolone, macrolide and tetracycline efflux proteins. Despite their lack of antibacterial activity, all extracts were able to potentiate antibiotics activities by as much as eight fold. Both the maceration and supercritical fluid extraction processes were adequate to obtain extracts with different biological activities according to their patterns of phenolic compounds. The data suggest that S. paludosum could be a valuable source of antioxidants and putative efflux pumps inhibitors.     

Effect of Al2Cu precipitates size and mass transport on the polarisation behaviour of age-hardened Al–Si–Cu–Mg alloys in 0.05 M NaCl

The electrochemical behaviour of age-hardened Al–Si–Cu–Mg alloys was investigated in a 0.05 M NaCl solution under controlled mass transport conditions using a rotating disk electrode. This work aimed at getting better understanding of the effect of the alloy microstructure, in particular the size distribution of Al₂Cu phase, on the corrosion behaviour of the alloy. Three different size distributions of the Al₂Cu phase were obtained through appropriate heat treatments. The cathodic reduction of oxygen was found to occur mainly on the Al₂Cu phases acting as preferential cathodes. Small sized Al₂Cu phases were found to promote at high rotation rates a transition from a 4 electron to a 2 electron dominated oxygen reduction mechanisms.     

Post-fire residual mechanical properties of concrete made with recycled concrete coarse aggregates

This paper presents results of an experimental study on the residual mechanical performance of concrete produced with recycled coarse aggregates, after being subjected to high temperatures. Four different concrete compositions were prepared: a reference concrete made with natural coarse aggregates and three concrete mixes with replacement rates of 20%, 50% and 100% of natural coarse aggregates by recycled concrete coarse aggregates. Specimens were exposed for a period of 1 h to temperatures of 400 °C, 600 °C and 800 °C, after being heated in accordance with ISO 834 time–temperature curve. After cooling down to ambient temperature, the following basic mechanical properties were then evaluated and compared with reference values obtained prior to thermal exposure: (i) compressive strength; (ii) tensile splitting strength; and (iii) elasticity modulus. Results obtained show that there are no significant differences in the thermal response and post-fire mechanical behaviour of concrete made with recycled coarse aggregates, when compared to conventional concrete.     

Aggregation Behavior of Perfluorononanoic Acid/Sodium Dodecyl Sulfate Mixtures

The mixed system of an anionic hydrocarbon surfactant, sodium dodecyl sulfate, and a perfluorinated surfactant, perfluorononanoic acid (PFNA), was investigated by a combination of methods. The critical micellar concentrations (CMC) were determined over a wide range of sample compositions by surface tension, conductivity and UV–visible spectrophotometry using N-(4-nitrophenyl)perfluorononanamide as a molecular probe. The values of CMC obtained by different techniques were in good agreement. In addition, the aggregation numbers were determined in the mixtures with a low content of hydrocarbon surfactant, by measuring the fluorescence quenching of pyrene. The hydrodynamic radii of the aggregates were estimated through the diffusion ordered ¹⁹F- and ¹H-NMR spectroscopy. The values obtained are in agreement with those expected according to the measured aggregation numbers. The analysis of the data with different aggregation models suggests the formation of a non-ideal mixed micelle that is enriched in the perfluorinated surfactant when its mole fraction increases, and that is practically formed by PFNA only at mole fractions higher than 0.8.     

ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

Synthesis,Computational Studies and Assessment of in Vitro Activity of Squalene Derivatives as Carbonic Anhydrase Inhibitors

We report novel molecules incorporating the nontoxic squalene scaffold and different carbonic anhydrase inhibitors (CAIs). Potent inhibitory action, in the low-nanomolar range, was detected against isoforms hCA II for sulfonamide derivatives, which proved to be selective against this isoform over the tumor-associate hCA IX and XII isoforms. On the other hand, coumarin derivatives showed weak potency but high selectivity against the tumor-associated isoform CA IX. These compounds are interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. In addition, an in silico study of inhibitor-bound hCA II revealed extensive interactions with the hydrophobic pocket of the active site and provided molecular insights into the binding properties of these new inhibitors.     

The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines

Breast (BrCa) and prostate (PCa) cancers are the most common malignancies in women and men, respectively. The available therapeutic options for these tumors are still not curative and have severe side effects. Therefore, there is an urgent need for more effective antineoplastic agents. Herein, BrCa, PCa, and benign cell lines were treated with two ionic liquids and two quinoxalines and functional experiments were performed—namely cell viability, apoptosis, cytotoxicity, and colony formation assays. At the molecular level, an array of gene expressions encompassing several molecular pathways were used to explore the impact of treatment on gene expression. Although both quinoxalines and the ionic liquid [C2OHMIM][Amp] did not show any effect on the BrCa and PCa cell lines, [C16Pyr][Amp] significantly decreased cell viability and colony formation ability, while it increased the apoptosis levels of all cell lines. Importantly, [C16Pyr][Amp] was found to be more selective for cancer cells and less toxic than cisplatin. At the molecular level, this ionic liquid was also associated with reduced expression levels of CPT2, LDHA, MCM2, and SKP2, in both BrCa and PCa cell lines. Hence, [C16Pyr][Amp] was shown to be a promising anticancer therapeutic agent for BrCa and PCa cell lines.