Meroterpenes from marine invertebrates: structures, occurrence, and ecological implications

Meroterpenes are widely distributed among marine organisms; they are particularly abundant within brown algae, but other important sources include microorganisms and invertebrates. In the present review the structures and bioactivities of meroterpenes from marine invertebrates, mainly sponges and tunicates, are summarized. More than 300 molecules, often complex and with unique skeletons originating from intra- and inter-​mol. cyclizations, and(or) rearrangements, are illustrated. The reported syntheses are mentioned. The issue of a potential microbial link to their biosynthesis is also shortly outlined

Being efficient to stay strong in a weak economy. The case of calabrian manufacturing firms

The aim of this work is to study the efficiency of firms operating in Calabria, a small and economically-lagging Italian region. The analysis is carried out by estimating a stochastic production frontier for an unbalanced panel of manufacturing firms which are observed over the 1998-2006 period. Results show that the efficiency score is, on average, about 60%. A declining trend is observed over the last three-year period, 2004-2006. Moreover, firm efficiency increases with firm age and when firms export. Inconclusive evidence is found for the role of investments in ICT and R&D. This is not very surprising given that private effort in technological activities is extremely low in Calabria (private R&D intensity was less than 0.075% of regional GDP in 2010)

Being efficient to stay strong in a weak economy. The case of calabrian manufacturing firms

The aim of this work is to study the efficiency of firms operating in Calabria, a small and economically-lagging Italian region. The analysis is carried out by estimating a stochastic production frontier for an unbalanced panel of manufacturing firms which are observed over the 1998-2006 period. Results show that the efficiency score is, on average, about 60%. A declining trend is observed over the last three-year period, 2004-2006. Moreover, firm efficiency increases with firm age and when firms export. Inconclusive evidence is found for the role of investments in ICT and R&D. This is not very surprising given that private effort in technological activities is extremely low in Calabria (private R&D intensity was less than 0.075% of regional GDP in 2010)

Further Investigation of the Mediterranean Sponge Axinella polypoides: Isolation of a New Cyclonucleoside and a New Betaine

An exhaustive exploration into the metabolic content of the Mediterranean sponge Axinella-polypoides resulted in the isolation of the new betaine 5 and the new cyclonucleoside 8. The structures of the new metabolites were elucidated by spectroscopic methods assisted by computational methods. The analysis also provided evidence that the sponge does not elaborate pyrrole-imidazole alkaloids (PIAs) but, interestingly, it was shown to contain two already known cyclodipeptides, compounds 9 (verpacamide A) and 10

Development of nature inspired antiplasmodial hits possessing the thiazinoquinone pharmacophore

Malaria accounts globally for more than 200 million new cases and 438,000 deaths per year. Since malaria is a disease of worldwide implications, combating it is one of the highest priority programs of the WHO. A worrisome increase in the number of fatal cases has been registered in recent years and it is principally due to the diffusion of multi-drug resistant strains of Plasmodium, making less effective the limited armamentarium of available drugs. Therefore, there is an urgent need of new antimalarial drugs with high efficacy against resistant strains and broad stage mode of action. To reach these challenging aims, the identification and selection of new lead compounds constitutes a crucial point. In this regard, nature remains an ever evolving resource. Recently, the antiplasmodial activity of marine secondary metabolites characterized by a quinone scaffold has been reported. In particular, it is worth to point out that a number of quinones have been shown to be effective antimalarials. The observed effects are most likely related to the most prominent chemical feature of these kind of molecules, that is their ability to undergo redox reaction i) shuttling electrons from reduced flavoproteins to acceptors such as hemoglobin-associated or free Fe(III)-protoporphyrin IX or ii) inhibiting the mitochondrial electron transport chain. In this context, recently, we were inspired by two marine metabolites Aplidinone A and B isolated from the Mediterranean ascidian Aplidium conicum, and we developed a series of synthetic analogues featuring the thiazinoquinone chemotype present in the natural metabolites with simplified side chains and different substituents. Manipulation of this chemical scaffold afforded additional analogues with improved pharmacological proprieties compared to the starting hits identified in the previous series

Insights into Cytotoxic Behavior of Lepadins and Structure Elucidation of the New Alkaloid Lepadin L from the Mediterranean Ascidian Clavelina lepadiformis

The chemical investigation of the Mediterranean ascidian Clavelina lepadiformis has led to the isolation of a new lepadin, named lepadin L, and two known metabolites belonging to the same family, lepadins A and B. The planar structure and relative configuration of the decahydroquinoline ring of lepadin L were established both by means of HR-ESIMS and by a detailed as extensive analysis of 1D and 2D NMR spectra. Moreover, microscale derivatization of the new alkaloid lepadin L was performed to assess the relative configuration of the functionalized alkyl side chain. Lepadins A, B, and L were tested for their cytotoxic activity on a panel of cancer cell lines (human melanoma [A375], human breast [MDA-MB-468], human colon adenocarcinoma [HT29], human colorectal carcinoma [HCT116], and mouse myoblast [C2C12]). Interestingly, a deeper investigation into the mechanism of action of the most cytotoxic metabolite, lepadin A, on the A375 cells has highlighted its ability to induce a strongly inhibition of cell migration, G2/M phase cell cycle arrest and a dose-dependent decrease of cell clonogenity, suggesting that it is able to impair self-renewing capacity of A375 cells

Assignment of the Absolute Configuration of Phosphoeleganin via Synthesis of Model Compounds

The full absolute configuration assignment of phosphoeleganin (1), a recently discovered marine-derived phosphorylated polyketide with protein tyrosine phosphatase 1B inhibitory activity, was achieved. It was based on the synthesis of model diasteroisomeric compounds of the C-8-C-12 segment portion of phosphoeleganin, chiral derivatization methods, and application of the universal NMR database concept

Phallusiasterol C, A New Disulfated Steroid from the Mediterranean Tunicate Phallusia fumigata

A new sulfated sterol, phallusiasterol C (1), has been isolated from the Mediterranean ascidian Phallusia fumigata and its structure has been determined on the basis of extensive spectroscopic (mainly 2D NMR) analysis. The possible role in regulating the pregnane X receptor (PXR) activity of phallusiasterol C has been investigated; although the new sterol resulted inactive, this study adds more items to the knowledge of the structure-PXR regulating activity relationships in the case of sulfated steroids

Investigating the antiparasitic potential of the marine sesquiterpene avarone, its reduced form avarol, and the novel semisynthetic thiazinoquinone analogue thiazoavarone

The chemical analysis of the sponge Dysidea avara afforded the known sesquiterpene quinone avarone, along with its reduced form avarol. To further explore the role of the thiazinoquinone scaffold as an antiplasmodial, antileishmanial and antischistosomal agent, we converted the quinone avarone into the thiazinoquinone derivative thiazoavarone. The semisynthetic compound, as well as the natural metabolites avarone and avarol, were pharmacologically investigated in order to assess their antiparasitic properties against sexual and asexual stages of Plasmodium falciparum, larval and adult developmental stages of Schistosomamansoni (eggs included), and also against promastigotes and amastigotes of Leishmania infantum and Leishmania tropica. Furthermore, in depth computational studies including density functional theory (DFT) calculations were performed. A toxic semiquinone radical species which can be produced starting both from quinone- and hydroquinone-based compounds could mediate the anti-parasitic effects of the tested compounds