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.

Chemical Profile and Bioactivity of Rubus idaeus L. Fruits Grown in Conventional and Aeroponic Systems.

Raspberry (Rubus idaeus L.) is a fruit of great interest due to its aroma, nutritional properties, and the presence of many bioactive compounds. However, differences among cultivation systems can affect its composition and, consequently, its potential bioactivity. Herein, for the first time, raspberries grown in an aeroponic system were investigated for their chemical profile and antioxidant and anti-inflammatory activity, as well as their enzyme (α-glucosidase and pancreatic lipase) inhibitory properties in comparison to wild and conventionally cultivated fruits. High-performance liquid chromatography coupled with diode array detection (HPLC-DAD) analyses revealed the presence of gallic acid, caffeic acid, chlorogenic acid, p-coumaric acid, ferulic acid, rutin, and catechin in all the samples. The extracts exhibited in vitro anti-inflammatory activity (inhibition of nitric oxide production) regardless of the cultivation method. Of particular interest is the ability of raspberries to inhibit pancreatic lipase. With the exception of the ß-carotene bleaching test, the raspberries grown in conventional and aeroponic systems were more active in terms of antioxidants than wild fruits, as evidenced by the ABTS (IC50 in the range 1.6-3.4 µg/mL), DPPH (IC50 in the range 8.9-28.3 µg/mL), and FRAP tests (24.6-44.9 µM Fe(II)/g). The raspberries from aeroponic cultivation were generally able to exert the same bioactivity as those obtained from both conventionally cultivated and wild fruits, supporting the consideration that in the future, this technology could reshape agriculture by mitigating resource constraints, fostering sustainable practices and increasing yields.

Multifunctional Membranes Based on ß-Glucans and Chitosan Useful in Wound Treatment.

In this work, bio-based membranes prepared using a crosslinked ß-glucans-chitosan dispersed in the chitosan matrix useful in promoting wound healing were studied for the first-time. Wound healing is a process that includes sequential steps designed to restore the structure and function of damaged cells and tissue. To minimize damage and the risk of infection during the healing process and to promote restoration of the integrity of damaged tissue, the wound should be dressed. Generally, according to their function in the wound, dressings are classified on the basis of type of material and physical form. The substances used to make a dressing are generally natural polymers such as hydrocolloids, alginates, polyurethane, collagen, chitosan, pectin and hyaluronic acid. The combination of polymeric substances, with antibacterial and antioxidant properties, could be exploited in the biomedical field for the development of biocompatible materials able to act as a barrier between the wound and the external environment, protecting the site from bacterial contamination and promoting healing. To this aim, bio-based membranes were prepared by the phase inversion induced by solvent evaporation, using the crosslinked ß-glucans-chitosan obtained by esterification reactions as a functional additive in the chitosan membrane. The reaction intermediates and the final products were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) while the morphological properties of membranes were analyzed using electronic scanning microscopy (SEM). The chemical bonding between chitosan and ß-glucans allowed for the obtainment of a better dispersion of the combined new material into the membrane's matrix and as a consequence, an enhanced antibacterial property evaluated through in vitro tests, with respect to the starting materials.

In vitro anti-proliferative and anti-bacterial properties of new C7 benzoate derivatives of pinocembrin.

In the present work, the in vitro anti-proliferative and anti-bacterial activities of three semi-synthetic benzoate pinocembrin derivatives, isolated from the aerial parts of Glycyrrhiza glabra L., were investigated. As occurs in most natural compounds, the bioavailability of pinocembrin is very poor, therefore it should be improved by chemical strategies aimed to prolong its shelf life and, consequently, its activity. On this basis, three benzoate derivatives of pinocembrin (a1-a3) were synthesised and assayed in order to ascertain their biological value. Among them, compound a1 showed the highest anti-proliferative activity on a wide panel of cancer cell lines, as well as low toxic effects on non-malignant breast cells. The calculated IC50 values in HeLa and SKBR3 cells were 8.5 and 12.7 µM, respectively. Briefly, a1 treatment increased ROS levels, induced mitochondrial membrane damage leading to necrotic death of HeLa cells. Moreover, a1 displayed a promising anti-bacterial activity.

5-(Carbamoylmethylene)-oxazolidin-2-ones as a Promising Class of Heterocycles Inducing Apoptosis Triggered by Increased ROS Levels and Mitochondrial Dysfunction in Breast and Cervical Cancer.

Oxazolidinones are antibiotics that inhibit protein synthesis by binding the 50S ribosomal subunit. Recently, numerous worldwide researches focused on their properties and possible involvement in cancer therapy have been conducted. Here, we evaluated in vitro the antiproliferative activity of some 5-(carbamoylmethylene)-oxazolidin-2-ones on MCF-7 and HeLa cells. The tested compounds displayed a wide range of cytotoxicity on these cancer cell lines, measured by MTT assay, exhibiting no cytotoxicity on non-tumorigenic MCF-10A cells. Among the nine tested derivatives, four displayed a good anticancer potential. Remarkably, OI compound showed IC50 values of 17.66 and 31.10 µM for MCF-7 and HeLa cancer cells, respectively. Furthermore, we assessed OI effect on the cell cycle by FACS analysis, highlighting a G1 phase arrest after 72 h, supported by a low expression level of Cyclin D1 protein. Moreover, mitochondrial membrane potential was reduced after OI treatment driven by high levels of ROS. These findings demonstrate that OI treatment can inhibit MCF-7 and HeLa cell proliferation and induce apoptosis by caspase-9 activation and cytochrome c release in the cytosol. Hence, 5-(carbamoylmethylene)-oxazolidin-2-ones have a promising anticancer activity, in particular, OI derivative could represent a good candidate for in vivo further studies and potential clinical use.

Exploring the anti-proliferative, pro-apoptotic, and antioxidant properties of Santolina corsica Jord. & Fourr. (Asteraceae).

AIMS: The bioactivities of Santolina corsica Jord. & Fourr. n-hexane (EHS) and methanol (EMS) extracts were evaluated in relation to their chemical profile. MAIN METHODS: EHS and EMS were analysed by gas chromatography-mass spectrometry () and high performance liquid chromatography-diode array detection (HPLC-DAD), respectively. Antioxidant activity was determined by ß-carotene bleaching, Ferric Reducing Activity Power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) tests. Nitric oxide (NO) production was assessed in LPS-stimulated RAW 264.7 cells. Anti-proliferative activity was evaluated by MTT assay on A549, HeLa, PC3, MCF-7, MDA-MB-231 cancer cells, and non-tumorigenic MCF10 A cells. Cell motility, migration and invasion were assessed by wound-healing scratch, migration and invasion assays, respectively. DNA fragmentation was tested by TUNEL assay. Cells morphology was studied by phase-contrast microscopy. Procaspase-8, -9, poly (ADP-ribose) polymerase and COX-2 expression levels were evaluated by immunoblotting analysis. KEY FINDINGS: Kaempferol-3-O-glucoside (5878.67 mg/100 g of extract), chlorogenic acid (746.11 mg/100 g), and rosmarinic acid (550.16 mg/100 g) were the dominant EMS constituents. EHS showed myrcene (18.86%) as the main compound, followed by palmitic acid methyl and ethyl esters (9.35 and 9.16%, respectively), ß-phellandrene (8.48%), and ar-curcumene (5.63%). Both extracts showed promising anti-proliferative activity on all tested cancer cells, without inducing cytotoxicity in non-tumorigenic cells MCF-10 A. Moreover, extracts inhibited motility, migration, and invasion of MDA-MB-231 cells, inducing apoptosis. EHS decreased NO production, showing anti-inflammatory activity. SIGNIFICANCE: S. corsica extracts might be potentially useful in cancer treatment, since reduce invasive and migratory potential of MDA-MB-231 cells triggering apoptosis.

Quercetin and derivatives: useful tools in inflammation and pain management.

Inflammation represents a very frequent condition in humans; it is often underestimated, making the problem an increasingly alarming phenomenon. For these reasons, conventional therapies are losing their effectiveness, leaving room for innovative therapies. In this field, natural products showed their efficacy in various diseases; and flavonoids, in particular quercetin, is known for its broad range of activities. In this review, we have highlighted its efficacy in various models of inflammation, focusing also on the activity of its semisynthetic derivatives, and those naturally present in plant extracts. Finally, the analgesic property of quercetin, intrinsically linked to its anti-inflammatory action, has been also evaluated, to investigate about an innovative approach to this interesting natural compound, such as analgesic remedial.

Synthesis and Antibacterial Activity of Polymerizable Acryloyloxyalkyltriethyl Ammonium Salts.

Invited for this month's cover are the collaborating groups at the University of Calabria (Unical, Italy)-Department of Chemistry and Chemical Technologies (CTC) and Department of Pharmacy and Health and Nutritional Sciences (PHNS), at the National Research Council (CNR, Italy), Institute on Membrane Technology (ITM), and at the Karlsruhe University of Applied Sciences (HSKA, Germany), Institute of Applied Research (IAR), which cooperated in the framework of the European Union's Horizon 2020 project "VicInAqua". The front cover shows the structure of an acryloxyalkyltrithylammonium (AATEA) cation, characterized by a polymerizable end, a long-chain alkyl linker, and a quaternary ammonium moiety. The bromide salts (AATEABs) have been synthesized by a two-step procedure carried out entirely under air without any need for chromatographic purifications. Some AATEABs have shown significant antimicrobial activity and represent useful precursors for the preparation of polymeric films with antimicrobial properties. Read the full text of the article at 10.1002/cplu.201700194.

Synthesis and Antibacterial Activity of Polymerizable Acryloyloxyalkyltriethyl Ammonium Salts.

This study reports an efficient and practical synthetic approach for the synthesis of a particularly important class of polymerizable quaternary ammonium salts (PQASs), that is, acryloxyalkyltriethylammonium bromides (AATEABs), which may find application as antimicrobial coatings for commercial membranes with antifouling and anti-biofouling properties, to be used for wastewater treatment. The synthetic method is based on a simple two-step procedure from commercially available substrates, entirely carried out under air and without any need for chromatographic purification. All the newly synthesized AATEABs were tested for their antimicrobial activity, and the results showed that AATEABs bearing an alkyl chain of 11 and particularly 12 carbon atoms possessed significant activity against Gram positive bacteria and yeast strains.

From Vegetable Waste to New Agents for Potential Health Applications: Antioxidant Properties and Effects of Extracts, Fractions and Pinocembrin from Glycyrrhiza glabra L. Aerial Parts on Viability of Five Human Cancer Cell Lines.

Glycyrrhiza glabra cultivation and harvesting produces substantial quantities of aerial parts as waste. With the aim to prospect an innovative valorization of these byproducts, the aerial parts were harvested in May and October and analyzed for their chemical profile, antioxidant properties, and effects on viability of five cancer cell lines. Pinocembrin was the main constituent. A significant protection of lipid peroxidation was observed with the May total extract (IC50 of 4.2 ± 0.4 µg/mL at 30 min of incubation). The effects on viability of HeLa, MCF-7, MDA-MB-231, Caco-2, and PC3 human cancer cells were investigated. All samples shown a remarkable activity with IC50 values below 25 µg/mL. Samples from plants harvested in May exhibited greater activity than those harvested in October. MCF-7 and HeLa were the most sensitive cells with IC50 in the range 2.73-3.01 and 3.28-5.53 µg/mL, respectively. G. glabra aerial parts represent a good source of valuable products.