Synthesis and anti-proliferative activity of a small library of 7-substituted 5H-pyrrole [1,2-a][3,1]benzoxazin-5-one derivatives

In this study, we investigate the anti-proliferative activity of a small library of 7-substituted 5H-pyrrolo[1,2-a][3,1]benzoxazin-5-one derivatives, against a panel of human cancer cell lines. We reported the synthesis of these compounds in a previous work. 7-Bromo-5H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-5-one showed a promising anti-proliferative effect. As starting material for Suzuki-Miyaura cross coupling reaction, it was selected for the design and the synthesis of six further derivatives, with the aim to better define structure-activity relationships. The anti-proliferative MTT assay revealed a dose-dependent reduction of cell viability, especially for 7-([1,1′-biphenyl]-4-yl)-5H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-5-one. Cell cycle and western blotting analysis suggested apoptosis as possible mechanism for its anti-proliferative activity. These preliminary results encourage our interest for further optimizations.     

Fusogenic domains in herpes simplex virus type 1 glycoprotein H

Infection of eukaryotic cells by enveloped viruses requires fusion between the viral envelope and the cellular plasma or endosomal membrane. The actual merging of the two membranes is mediated by viral envelope glycoproteins, which generally contain a highly hydrophobic region termed the fusion peptide. The entry of herpesviruses is mediated by three conserved proteins: glycoproteins B, H (gH), and L. However, how fusion is executed remains unknown. Herpes simplex virus type 1 gH exhibits features typical of viral fusion glycoproteins, and its ectodomain seems to contain a putative internal fusion peptide. Here, we have identified additional internal segments able to interact with membranes and to induce membrane fusion of large unilamellar vesicles. We have applied the hydrophobicity-at-interface scale proposed by Wimley and White (Wimley, W. C., and White, S. H. (1996) Nat. Struct. Biol. 3, 842-848) to identify six hydrophobic stretches within gH with a tendency to partition into the membrane interface, and four of them were able to induce membrane fusion. Experiments in which equimolar mixtures of gH peptides were used indicated that different fusogenic regions may act in a synergistic way. The functional and structural characterization of these segments suggests that herpes simplex virus type 1 gH possesses several fusogenic internal peptides that could participate in the actual fusion event.     

Phytochemical and Biological Characterization of Methanolic Extracts from Rumex algeriensis and Rumex tunetanus

The present study is aimed at the evaluation of the phytochemical profile and the biochemical properties of methanolic extracts obtained from different parts of Rumex algeriensis and Rumex tunetanus, two relict species limited to the North Africa. Phytochemical analyses of these extracts were performed using standard colorimetric procedures, HPLC‐DAD, and HPLC‐DAD‐ESI/MS, and their antioxidant/free radical scavenging capability was estimated through several in vitro cell‐free assays. Moreover, the anti‐inflammatory potential of these extracts was demonstrated in an in vitro model of acute intestinal inflammation using differentiated Caco‐2 cells. The results showed that all the extracts appeared endowed with excellent antioxidant/free radical scavenging properties. In particular, the extracts from both R. algeriensis and R. tunetanus flowers, and that from R. algeriensis stems were characterized by a remarkable SOD‐like and NO‐scavenging activity, as well as by the capability to protect albumin against HClO‐induced degradation. Furthermore, the extracts from flowers of both Rumex species, as well as R. algeriensis stems, showed an anti‐inflammatory effect in intestinal epithelial cells, as demonstrated by the inhibition of TNF‐α‐induced gene expression of IL‐6 and IL‐8. In conclusion, R. algeriensis and R. tunetanus have shown to be potential sources of bioactive products to be used in the prevention and treatment of pathologies related to oxidative stress and inflammation.     

Evaluation of Antioxidant,Anti-Inflammatory and Antityrosinase Potential of Extracts from Different Aerial Parts of Rhanterium suaveolens from Tunisia

The genus Rhanterium (Asteraceae) is a widely distributed medicinal plant throughout western North Africa and some Rhanterium species are used in folk medicine. The aim of research was to investigate methanolic extracts from different parts (flowers, leaves, and stems) of Tunisian Rhanterium suaveolens as potential sources of bioactive products useful for healthy purposes. In particular, were analyzed the phenolic composition of these extracts and their antioxidant, anti-inflammatory, and anti-tyrosinase properties. The phytochemical analyses were performed using standard colorimetric procedures, HPLC-DAD and HPLC-DAD-ESI-MS. Then, several in vitro cell-free assays have been used to estimate the antioxidant/free radical scavenging capability of the extracts. Moreover, in vitro, and in vivo anti-melanogenesis activities of these extracts were tested, respectively, with the tyrosinase inhibition assay and the Zebrafish embryo model. Finally, the anti-inflammatory potential of these extracts in an in vitro model of acute intestinal inflammation in differentiated Caco-2 cells was evaluated. The R. suaveolens extracts under study appeared particularly rich in flavonols and hydroxycinnamic acids and all extracts appeared endowed with good antioxidant/free radical scavenging properties, being the flower extracts slightly more active than the others. Moreover, R. suaveolens flowers extract was able to inhibit in vitro tyrosinase activity and exhibited bleaching effects on the pigmentation of zebrafish embryos. Furthermore, all extracts showed good anti-inflammatory activity in intestinal epithelial cells as demonstrated by the inhibition of TNF-α-induced gene expression of IL-6 and IL-8. R. suaveolens aerial parts may be considered as a potential source of whitening agents, as well as of agents for the treatment of disorders related to oxidative stress and inflammation.     

Efficient succinic acid production from high-sugar-content beverages by Actinobacillus succinogenes

This study presents the production of succinic acid (SA) by Actinobacillus succinogenes using high-sugar-content beverages (HSCBs) as feedstock. The aim of this study was the valorization of a by-product stream from the beverage industry for the production of an important building block chemical, such as SA. Three types of commercial beverages were investigated: fruit juices (pineapple and ace), syrups (almond), and soft drinks (cola and lemon). They contained mainly glucose, fructose, and sucrose at high concentration—between 50 and 1,000 g/L. The batch fermentation tests highlighted that A. succinogenes was able to grow on HSCBs supplemented with yeast extract, but also on the unsupplemented fruit juices. Indeed, the bacteria did not grow on the unsupplemented syrup and soft drinks because of the lack of indispensable nutrients. About 30–40 g/L of SA were obtained, depending on the type of HSCB, with yield ranging between 0.75 and 1.00 g_SA/g_S. The prehydrolysis step improved the fermentation performance: SA production was improved by 6–24%, depending on the HSCB, and sugar conversion was improved of about 30–50%.