Pinofuranoxins A and B, Bioactive Trisubstituted Furanones Produced by the Invasive Pathogen Diplodia sapinea

Two new bioactive trisubstituted furanones, named pinofuranoxins A and B (1 and 2), were isolated from Diplodia sapinea, a worldwide conifer pathogen causing severe disease. Pinofuranoxins A and B were characterized essentially by NMR and HRESIMS spectra, and their relative and absolute configurations were assigned by NOESY experiments and computational analyses of electronic circular dichroism spectra. They induced necrotic lesions on Hedera helix L., Phaseolus vulgaris L., and Quercus ilex L. Compound 1 completely inhibited the growth of Athelia rolfsii and Phytophthora cambivora, while 2 showed antioomycetes activity against P. cambivora. In the Artemia salina assay both toxins showed activity inducing larval mortality

Cytotoxicity and Antiviral Properties of Alkaloids Isolated from Pancratium maritimum

Ten Amaryllidaceae alkaloids (AAs) were isolated for the first time from Pancratium maritimum collected in Calabria region, Italy. They belong to different subgroups of this family and were identi-fied as lycorine, which is the main alkaloid, 9-O-demethyllycorine, haemanthidine, haemanthamine, 11-hydroxyvittatine, homolycorine, pancracine, obliquine, tazettine and vittatine. Haemanthidine was isolated as a scalar mixture of two 6-epimers, as already known also for other 6-hydroxycrinine alkaloids, but for the first time they were separated as 6,11-O,O′-di-p-bromobenzoyl esters. The evaluation of the cytotoxic and antiviral potentials of all isolated compounds was undertaken. Ly-corine and haemanthidine showed cytotoxic activity on Hacat cells and A431 and AGS cancer cells while, pancracine exhibited selective cytotoxicity against A431 cells. We uncovered that in addition to lycorine and haemanthidine, haemanthamine and pancracine also possess antiretroviral abilities, inhibiting pseudotyped human immunodeficiency virus (HIV)−1 with EC50 of 25.3 µM and 18.5 µM respectively. Strikingly, all the AAs isolated from P. maritimum were able to impede dengue virus (DENV) replication (EC50 ranged from 0.34–73.59 µM) at low to non-cytotoxic concentrations (CC50 ranged from 6.25 µM to >100 µM). Haemanthamine (EC50 = 337 nM), pancracine (EC50 = 357 nM) and haemanthidine (EC50 = 476 nM) were the most potent anti-DENV inhibitors. Thus, this study uncovered new antiviral properties of P. maritimum isolated alkaloids, a significant finding that could lead to the development of new therapeutic strategies to fight viral infectious diseases

Cardiac and Vascular Synergic Protective Effect of Olea europea

This study was aimed at investigating the cardiovascular effects of an Olea europea L. leaf extract (OEE), of a Hibiscus sabdariffa L. flower extract (HSE), and of their 13 : 2 w/w mixture in order to assess their cardiac and vascular activity. Both extracts were fully characterized in their bioactive compounds by HPLC-MS/MS analysis. The study was performed using primary vascular endothelial cells (HUVECs) to investigate the antioxidant and cytoprotective effect of the extracts and their mixture and isolated guinea-pig left and right atria and aorta to evaluate the inotropic and chronotropic activities and vasorelaxant properties. In cultured HUVECs, OEE and HSE reduced intracellular reactive oxygen species formation and improved cell viability, following oxidative stress in dose-dependent manner. OEE and HSE exerted negative inotropic and vasorelaxant effects without any chronotropic property. Interestingly, the mixture exerted higher cytoprotective effects and antioxidant activities. Moreover, the mixture exerted an inotropic effect similar to each single extract, while it revealed an intrinsic negative chronotropic activity different from the single extract; its relaxant activity was higher than that of each single extract. In conclusion OEE and HSE mixture has a good potential for pharmaceutical and nutraceutical application, thanks to the synergistic effects of the single phytochemicals

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Bioactive metabolites produced by pathogenic fungi of forest plants

Pathogenic fungi are the main causes of forest plant disease. They induce alterations during developmental stages and the development of diseases, in particular canker, which determine huge economic and environmental losses, especially for plant nurseries and wood industries. Fungal-plant host interactions represent biochemically complex systems that are being studied also by metabolites involved. Pathogenic fungi are able to produce phytotoxins, i.e. secondary metabolites, which are involved at different stages of plant pathogenesis. Considering the strong economic and ecological impact of forest plant diseases, the study of the plant-pathogen interaction and the metabolites involved is of remarkable importance. The aim of this PhD project has been on the investigation of phytotoxins produced by forest plants fungal pathogens. Culture filtrates have been obtained from Hymenoscyphus fraxineus, responsible of ash dieback, from Fimetariella rabenhorstii and Stilbocrea macrostoma, two fungi associated to Quercus brantii decline, from Diplodia olivarum, an aggressive pathogen of different plants in Italy, from Alternaria argyroxiphii, responsible of leaf spot of mahogany (Khaya senegalensis), and from Diplodia sapinea, associated to canker of Tunisian pine (Pinus pinaster). They have been exhaustively extracted and, the corresponding phytotoxic extracts have been purified to obtain metabolites by bio-guided chromatographic processes. A new metabolite, named hyfraxinic acid, has been isolated and characterized from the culture filtrates of H. fraxineus together with four furano diterpenoids. Among them, the relative and the absolute configurations have been assigned to 1-deoxyviridiol by crystallographic analyses and by the application of the advanced Mosher’s method. The new compound has been showed the most toxic effect in the phytotoxic assay. A new chromenone and a new benzophenone, named rabenchromenone and rabenzophenone, have been isolated from the culture filtrate of F. rabenhostrii together with moniliphenone and coniochaetone A. The absolute configuration of rabenchromenone has been determined by application of electronic circular dichroism (ECD) spectroscopy supported by quantum mechanical calculations compared with the experimental spectrum. In the leaf puncture assay, rabenzophenone has proved to be the most toxic compound. From the culture filtrate of S. macrostoma, three well-known compounds have been identified as 2,5-dihydroxymethylfuran, 5-hydroxymethyl-2-furaldehyde and tyrosol. All metabolites have been phytotoxic in the biological assay, but in particular the phytotoxicity of the two furan derivatives has been concentration-dependent. A new cleistanthane nor-diterpenoid, named olicleistanone, has been isolated and characterized from the culture filtrate of D. olivarum, which has showed to be a racemate. Other four pimarane diterpenoids and an isocoumarin has been identified. In the bioassays, olicleistanone has been showed a zootoxic activity against Artemia salina L. From the culture filtrate of A. argyroxiphii, three new metabolites, named argyrotoxins A-C, have been isolated and characterized. The absolute configuration of argyrotoxin A has been determined by quantum chemical calculations and electronic circular dichroism experiments using a chiroptical probe. Other known compounds have been identified as porritoxinol, its phthalide, the phthalide carboxylic acid derivative, zinniol, alternariol and its 4-methyl ether. In the leaf puncture assay, argyrotoxin A and B have been phytotoxic on Phaseolus vulgaris L. leaves only. Two new trisubstituted furanones, named pinofuranoxins A and B, have been isolated and characterized from the culture filtrate of D. sapinea. Their relative and absolute configurations have been assigned by NOESY experiment and by computational and ECD analyses, respectively. Both compounds have presented phytotoxic, antifungal and zootoxic activities and in details pinofuranoxin A has been more active than pinofuranoxin B

New lithium ion batteries exploiting conversion/alloying anode and LiFe0.25Mn0.5Co0.25PO4 olivine cathode

New Li-ion cells are formed by combining a LiFe0.25Mn0.5Co0.25PO4 olivine cathode either with Sn-Fe2O3-C or with Sn-C composite anodes. These active materials exhibit electrochemical properties very attractive in view of practical use, including the higher working voltage of the LiFe0.25Mn0.5Co0.25PO4 cathode with respect to conventional LiFePO4, as well as the remarkable capacity and rate capability of Sn-Fe2O3-C and Sn-C anodes. The stable electrode/electrolyte interfaces, demonstrated by electrochemical impedance spectroscopy, along with proper mass balancing and anode pre-lithiation, allow stable galvanostatic cycling of the full cells. The two batteries, namely Sn-Fe2O3-C/LiFe0.25Mn0.5Co0.25PO4 and Sn-C/LiFe0.25Mn0.5Co0.25PO4, reversibly operate revealing promising electrochemical features in terms of delivered capacity, working voltage and stability, thus suggesting these electrodes combinations as suitable alternatives for an efficient energy storage

Lithium-ion batteries for sustainable energy storage: Recent advances towards new cell configurations

The recent advances in the lithium-ion battery concept towards the development of sustainable energy storage systems are herein presented. The study reports on new lithium-ion cells developed over the last few years with the aim of improving the performance and sustainability of electrochemical energy storage. Alternative chemistries involving anode, cathode and electrolyte components are herein recalled in order to provide an overview of state-of-the-art lithium-ion battery systems, with particular focus on the cell configurations currently proposed at the laboratory scale. Hence, the review highlights the main issues related to full cell assembly, which have been tentatively addressed by a limited number of reports, while many papers describe materials investigation in half-cells, i.e., employing lithium metal anodes. The new battery prototypes here described are evaluated in terms of their electrochemical performances, cell balance, efficiency and cycle life. Finally, the applicability of these suitable energy storage systems is evaluated in the light of their most promising characteristics, thus outlining a conceivable scenario for new generation, sustainable lithium-ion batteries

Advances in the Chemical and Biological Characterization of Amaryllidaceae Alkaloids and Natural Analogues Isolated in the Last Decade

Amaryllidaceae are bulbous wild and cultivated plants well known for their beautiful flowers and pharmaceutical applications, essentially due to the alkaloids and flavonoids content. Hundreds of alkaloids have been isolated until now and several scientific publications reported their sources, chemical structures, and biological activities. During the last decade, some unstudied Amaryllidaceae plants were the object of in-depth investigations to isolate and chemically and biologically characterize new and already known alkaloids as well as some analogues. This review describes the isolation and chemical and biological characterization of the Amaryllidaceae alkaloids, and their analogues obtained in the last decade, focusing the discussion on the new ones

Argyrotoxins A-C, a trisubstituted dihydroisobenzofuranone, a tetrasubstituted 2-hydroxyethylbenzamide and a tetrasubstitutedphenyl trisubstitutedbutyl ether produced by Alternaria argyroxiphii, the causal agent of leaf spot on African mahogany trees (Khaya senegalensis)

Three previously undescribed metabolites named argyrotoxins A-C, were isolated, together with the well known porritoxinol, its closely related phthalide, a phthalide derivative, zinniol, alternariol and its 4-methyl ether from Alternaria argyroxiphii E.G. Simmons & Aragaki, the causal agent of leaf spot on African mahogany trees, Khaya senegalensis A. Juss. (Meliaceae). The known compounds were identified comparing their physical and spectroscopic properties to those previously reported in literature. Argyrotoxins A-C were characterized essentially by NMR (1H, 13C, COSY, HSQC, HMBC and NOESY NMR spectra) and HRESIMS spectra as 4-(7-methoxy-6-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yloxy)-2-methyl-butyric acid, 5-but-2-enyloxy-N-(2-hydroxyethyl)-2-hydroxymethyl-3-methoxy-4-methyl-benzamide and 1-(5-(hydroxymethyl)-3-methoxy-4-(methoxymethyl)-2-methylphenoxy)-3-methylbutane-2,3-diol, respectively. The absolute configuration of argyrotoxin A was determined through electronic circular dichroism, by applying the biphenyl chiroptical probe approach. The phytoxicity of all metabolites isolated was evaluated by leaf puncture assay at concentration of 1 mg/mL. Zinniol proved to be the most active compound causing necrotic lesions on young leaves of Hedera elix L., Phaseolus vulgaris L. and Quercus ilex L. Argirotoxins A and B were found active, to a minor extent, on Phaseolus vulgaris L. leaves, while porritoxinol exhibited activity on holm oak leaves. The other secondary metabolites herein reported for A. argyroxiphii were inactive

Phytotoxic metabolites from Stilbocrea macrostoma, a fungal pathogen of Quercus brantii in Iran

Two phytotoxic furan derivatives were isolated, together with the well-known fungal and plant phytotoxin tyrosol, from the culture filtrates of Stilbocrea macrostoma. This fungal pathogen isolated from Quercus brantii trees induced wood necrosis and decline symptoms on the host plant in Iran. The two furan derivatives, isolated for the first time from Stilbocrea macrostoma, were identified by spectroscopic methods (essentially 1 D and 2 D 1H and 13C NMR and ESIMS spectroscopy) as 5-hydroxymethylfuraldehyde and 2,5-dihydroxymethylfuran. The phytotoxic activity of the three metabolites was evaluated by leaf puncture assay on holm oak (Quercus ilex L.) and tomato (Lycopersicon esculentum L.) leaves. All compounds induced necrosis on holm oak leaves while very low toxicity was showed against tomato leaves. The two furan derivatives were more toxic than tyrosol and particularly 5-hydroxymethylfuraldehyde was the most phytotoxic compound