analysis of anti biofilm activities of extracts from marine invertebrate collected from a zmir bay eastern aegean sea

In the maritime industry, biofouling is a severe problem and represents a serious matter of economic losses worldwide

Alkaloids from marine ascidians

About 300 alkaloid structures isolated from marine ascidians are discussed in term of their occurrence, structural type and reported pharmacol. activity. Some major groups (e.g., the lamellarins and the ecteinascidins) are discussed in detail, highlighting their potential as therapeutic agents for the treatment of cancer or viral infections

The ascidian-derived metabolites with antimicrobial properties

Among the sub-phylum of Tunicate, ascidians represent the most abundant class of marine invertebrates, with 3000 species by heterogeneous habitat, that is, from shallow water to deep sea, already reported. The chemistry of these sessile filter-feeding organisms is an attractive reservoir of varied and peculiar bioactive compounds. Most secondary metabolites isolated from ascidians stand out for their potential as putative therapeutic agents in the treatment of several illnesses like microbial infections. In this review, we present and discuss the antibacterial activity shown by the main groups of ascidian-derived products, such as sulfur-containing compounds, meroterpenes, alkaloids, peptides, furanones, and their derivatives. Moreover, the direct evidence of a symbiotic association between marine ascidians and microorganisms shed light on the real producers of many extremely potent marine natural compounds. Hence, we also report the antibacterial potential, joined to antifungal and antiviral activity, of metabolites isolated from ascidian-associate microorganisms by culture-dependent methods

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

Antiplasmodial activity of p-substituted benzyl thiazinoquinone derivatives and their potential against parasitic infections

Malaria is a life-threatening disease and, what is more, the resistance to available antimalarial drugs is a recurring problem. The resistance of Plasmodium falciparum malaria parasites to previous generations of medicines has undermined malaria control efforts and reversed gains in child survival. This paper describes a continuation of our ongoing efforts to investigate the effects against Plasmodium falciparum strains and human microvascular endothelial cells (HMEC-1) of a series of methoxy p-benzyl-substituted thiazinoquinones designed starting from a pointed antimalarial lead candidate. The data obtained from the newly tested compounds expanded the structure-activity relationships (SARs) of the thiazinoquinone scaffold, indicating that antiplasmodial activity is not affected by the inductive effect but rather by the resonance effect of the introduced group at the para position of the benzyl substituent. Indeed, the current survey was based on the evaluation of antiparasitic usefulness as well as the selectivity on mammalian cells of the tested p-benzyl-substituted thiazinoquinones, upgrading the knowledge about the active thiazinoquinone scaffold

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