Dimeric phenanthrenoids: possible biogenetic pathway and missing compounds.

Secondary metabolites extracted from plants have historically been critical for drug discovery, but their isolation involves expensive and complicated procedures in terms of time and labor resources. Thus, the biogenetic pathway offers the possibility of identifying specific compounds that have not yet been isolated and predicting their isolation from specific natural sources. In plants, biphenanthrenes represent a relatively small group of aromatic secondary metabolites that are considered as important taxonomic markers with promising biological activities. To date, 38 mixed phenanthrenoid dimers have been identified, the biosynthesis of which involves the radical coupling of the two subunits, namely, a phenanthrene and a dihydrophenanthrene. For each of the compounds, it is possible to identify the single phenanthrenic and dihydrophenanthrenic units constituting the considered dimer. Based on the biogenetic pathway, it is possible to identify 19 phenanthrenes and 17 dihydrophenanthrenes, and to distinguish those already known from those not yet isolated. By comparing the results of the possible biosynthetic pathway for each compound with the data in the literature, it is possible to identify three known phenanthrenes and seven known dihydrophenanthrenes, as well as eleven new phenanthrenes and five new dihydrophenanthrenes, and to identify from which plant it is possible to isolate them. This could direct the work of researchers seeking to identify known or new molecules useful for their possible biological properties, and ultimately, to confirm the veracity of the proposed and generally accepted biosynthetic pathway.

A pan-influenza antibody inhibiting neuraminidase via receptor mimicry.

Rapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies predominantly to the highly variable head region of haemagglutinin and their effectiveness is limited by viral drift1 and suboptimal immune responses2. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits the enzymatic activity of all group 1 and group 2 IAVs, as well as Victoria/2/87-like, Yamagata/16/88-like and ancestral IBVs. FNI9 broadly neutralizes seasonal IAVs and IBVs, including the immune-evading H3N2 strains bearing an N-glycan at position 245, and shows synergistic activity when combined with anti-haemagglutinin stem-directed antibodies. Structural analysis reveals that D107 in the FNI9 heavy chain complementarity-determinant region 3 mimics the interaction of the sialic acid carboxyl group with the three highly conserved arginine residues (R118, R292 and R371) of the neuraminidase catalytic site. FNI9 demonstrates potent prophylactic activity against lethal IAV and IBV infections in mice. The unprecedented breadth and potency of the FNI9 monoclonal antibody supports its development for the prevention of influenza illness by seasonal and pandemic viruses.

Phenanthrene Dimers: Promising Source of Biologically Active Molecules.

To date, just over a hundred phenanthrenoid dimers have been isolated. Of these, forty-two are completely phenanthrenic in nature. They are isolated from fourteen genera of different plants belonging to only five families, of which Orchidaceae is the most abundant source. Other nine completely acetylated and five methylated dimers were also defined, which were effective in establishing the position of the free hydroxyls of the corresponding natural products, from which they were obtained by semi-synthesis. Structurally, they could be useful chemotaxonomic markers considering that some substituents are typical of a single-family, such as the vinyl group for Juncaceae. From a biogenetic point of view, it is thought that these compounds derive from the radical coupling of the corresponding phenanthrenes or by dehydrogenation of the dihydrophenanthrenoid analogs. Phenanthrenes or dihydroderivatives possess different biological activities, e.g., antiproliferative, antimicrobial, antiinflammatory, antioxidant, spasmolytic, anxiolytic, and antialgal effects. The aim of this review is to summarize the occurrence of phenanthrene dimers in the different natural sources and give a comprehensive overview of their structural characteristics and biological activities.

Silymarin from Silybum marianum by Naviglio's extractor: a new and very efficient approach.

The aim of this work is to compare new and traditional extraction methods to obtain silymarin from Silybum marianum, a biennial herbaceous plant of the Asteraceae family, present throughout the Mediterranean basin and used to treat several diseases. Silymarin primarily contains flavonolignans and flavonoids and is used in some pharmaceutical preparations to improve of liver function and as a protective against some hepatotoxins. In six extracts obtained by new and traditional extraction methods, the total contents of silymarin and its main flavonolignans, total phenols and condensed tannins were evaluated in addition to their respective antioxidant capacities. By the Naviglio extractor, that is a rapid solid-liquid dynamic extraction method, it is possible to obtain a fraction quantitatively more abundant than other methods, and with a lower content of tannins and phenolic compounds but with a higher content of flavonolignans, rare and expensive, and therefore easier to separate and purify.

Evaluation of tourism impact on soil metal accumulation through single and integrated indices.

Recently, surface soils of remote or protected areas, that receive pollutants from the surroundings or in situ activities through dry and wet deposition, exceed the baseline content of heavy metals. In the last decades, the use of single and integrated indices is a powerful tool to process, analyze and convey information about metal accumulation degree for decision makers to better manage protected areas. Single indices provide information about only one metal, whereas the integrated ones give a holistic evaluation. The aim of the research was to assess the temporal trends of three single (Contamination Factor, Enrichment Factor and Geo-accumulation Index) and two integrated (Pollution Load Index, Nemerow index) indices in order to evaluate if the touristic impact caused soil metal (Cr, Cu, Ni and Pb) accumulation. In autumn 2016 and in spring 2016 and 2017, the surface soils (0-10 cm) were collected at eight sites inside the Vesuvius National Park (Southern Italy), characterized by intense tourism from spring to autumn. The metal concentrations were measured in the soils and used to calculate the indices. In addition, the Ecological Risk Factor was calculated and the phytotoxicological assays were performed. The findings showed that the surface soils of the Vesuvius National Park were polluted by Cr, Cu, Ni and Pb, according to both single and integrated indices. The touristic impact would seem to be the main cause of soil metal accumulation, as the highest values of the calculated indices were detected for samples collected at the end of the touristic season and the lowest at the beginning of the touristic season. Anyway, Cu and Pb would seem also to derive by ex situ anthropogenic sources, whereas Cr and Ni also by natural sources, such as spontaneous fires and substrate weathering. Finally, the soils showed phytotoxic effects and low ecological risks.

Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae.

Emerging multidrug-resistant bacteria are a challenge for modern medicine, but how these pathogens are so successful is not fully understood. Robust antibacterial vaccines have prevented and reduced resistance suggesting a pivotal role for immunity in deterring antibiotic resistance. Here, we show the increased prevalence of Klebsiella pneumoniae lipopolysaccharide O2 serotype strains in all major drug resistance groups correlating with a paucity of anti-O2 antibodies in human B cell repertoires. We identify human monoclonal antibodies to O-antigens that are highly protective in mouse models of infection, even against heavily encapsulated strains. These antibodies, including a rare anti-O2 specific antibody, synergistically protect against drug-resistant strains in adjunctive therapy with meropenem, a standard-of-care antibiotic, confirming the importance of immune assistance in antibiotic therapy. These findings support an antibody-based immunotherapeutic strategy even for highly resistant K. pneumoniae infections, and underscore the effect humoral immunity has on evolving drug resistance.

Triterpenoids from Gymnema sylvestre and their pharmacological activities.

Because plants are estimated to produce over 200,000 metabolites, research into new natural substances that can be used in the pharmaceutical, agrochemical and agro-industrial production of drugs, biopesticides and food additives has grown in recent years. The global market for plant-derived drugs over the last decade has been estimated to be approximately 30.69 billion USD. A relevant specific example of a plant that is very interesting for its numerous pharmacological properties, which include antidiabetic, anticarcinogenic, and neuroprotective effects is Gymnema sylvestre, used as a medicinal plant in Asia for thousands of years. Its properties are attributed to triterpenoidic saponins. In light of the considerable interest generated in the chemistry and pharmacological properties of G. sylvestre triterpenes and their analogues, we have undertaken this review in an effort to summarise the available literature on these promising bioactive natural products. The review will detail studies on the isolation, chemistry and bioactivity of the triterpenoids, which are presented in the tables. In particular the triterpenoids oxidised at C-23; their isolation, distribution in different parts of the plant, and their NMR spectral data; their names and physico-chemical characterisation; and the biological properties associated with these compounds, with a focus on their potential chemotherapeutic applications.