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Marine ecosystems cover more than 70% of the globe's surface. These habitats are occupied by a great diversity of marine organisms that produce highly structural diverse metabolites as a defense mechanism. In the last decades, these metabolites have been extracted and isolated in order to test them in different bioassays and assess their potential to fight human diseases. Since traditional extraction techniques are both solvent- and time-consuming, this review emphasizes alternative extraction techniques, such as supercritical fluid extraction, pressurized solvent extraction, microwave-assisted extraction, ultrasound-assisted extraction, pulsed electric field-assisted extraction, enzyme-assisted extraction, and extraction with switchable solvents and ionic liquids, applied in the search for marine compounds. Only studies published in the 21 st century are considered. © 2015 by the authors; licensee MDPI. ; The authors are grateful for the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through project Pest-C/EQB/LA0006/2013, to financial support from the European Union (FEDER funds) under the framework of QREN through Project NORTE-07-0124-FEDER-000069, to CYTED Programme (Ref. 112RT0460) CORNUCOPIA Thematic Network and project AGL2011-23690 (CICYT). Clara Grosso thanks FCT for the FCT Investigator (IF/01332/2014). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI). ; Peer Reviewed

Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, some examples of neuroprotective drugs and neurotoxins will be discussed. Their role in neuroscience research and development of new therapies targeting the central nervous system will be addressed, with particular focus on neuroinflammation and neurodegeneration. In addition, the neuronal growth promoted by marine drugs, as well as the recent advances in neural tissue engineering, will be highlighted. ; The authors are grateful to the financial support from the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through project Pest-C/EQB/LA0006/2013 and from the European Union (FEDER funds) under the framework of QREN through Project NORTE-07–0124-FEDER-000069, to CYTED Programme (Ref. 112RT0460) CORNUCOPIA Thematic Network and project AGL2011–23690 (CICYT). Clara Grosso thanks FCT for the Post-Doc fellowship (SFRH/BPD/63922/2009). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI) ; Peer reviewed

The recent interest in wild edible plants is associated with their health benefits, which are mainly due to their richness in antioxidant compounds, particularly phenolics. Nevertheless, some of these compounds are metabolized after ingestion, being transformed into metabolites frequently with lower antioxidant activity. The aim of the present study was to evaluate the influence of the digestive process on the total phenolic contents and antioxidant activity of extracts from four wild edible plants used in the Mediterranean diet (Beta maritima L., Plantago major L., Oxalis pes-caprae L. and Scolymus hispanicus L.). HPLC-DAD analysis revealed that S. hispanicus is characterized by the presence of caffeoylquinic acids, dicaffeoylquinic acids and flavonol derivatives, P. major by high amounts of verbascoside, B. maritima possesses 2,4-dihydroxybenzoic acid, 5-O-caffeoylquinic acid, quercetin derivatives and kaempferol-3-O-rutinoside, and O. pes-caprae extract contains hydroxycinnamic acids and flavone derivatives. Total phenolic contents were determined by Folin-Ciocalteu assay, and antioxidant activity by the ABTS, DPPH, ORAC and FRAP assays. Phenolic contents of P. major and S. hispanicus extracts were not affected by digestion, but they significantly decreased in B. maritima after both phases of digestion process and in O. pes-caprae after the gastric phase. The antioxidant activity results varied with the extract and the method used to evaluate the activity. Results showed that P. major extract has the highest total phenolic contents and antioxidant activity, with considerable values even after digestion, reinforcing the health benefits of this species. ; European Union (FEDER funds through COMPETE)European Union (EU) ; European Union (FEDER)European Union (EU) ; Programa de Cooperacion Interreg V-A Espana - Portugal (POCTEP) 2014-2020 [0377_IBERPHENOL_6_E] ; project INTERREG - MD. Net: When Brand Meets People ; FCT Portuguese Foundation for Science and Technology

A library of N-protected dehydroamino acids, namely dehydroalanine, dehydroaminobutyric acid and dehydrophenylalanine derivatives, was screened in three human cancer cell lines [(lung (A549), gastric (AGS) and neuroblastoma (SH-SY5Y)] in order to characterize their toxicological profile and identify new molecules with potential anticancer activity. Results showed N-protected dehydrophenylalanine and dehydroaminobutyric acid derivatives have no or low toxicity for all tested cell lines. The N-protected dehydroalanines exhibit significant toxic effects and the AGS and SH-SY5Y cells were significantly more vulnerable than A549 cells. Four α,β- dehydroalanine derivatives, with IC50 < 62.5 μM, were selected to investigate the pathways by which these compounds promote cell death. All compounds, at their IC50 concentrations, were able to induce apoptosis in both AGS and SH-SY5Y cell lines. In both cell lines, loss of mitochondrial membrane potential (ΔΨm) was found and caspase activity was increased, namely endoplasmic reticulum-resident caspase-4 in AGS cells and caspase-3/7 in SH-SY5Y cells. When evaluated in a non-cancer cell line, the molecules displayed no to low toxicity, thus suggesting some degree of selectivity for cancer cells. The results indicate that α,β-dehydroalanine derivatives can be considered a future resource of compounds able to work as anticancer drugs. ; This work received financial support from National Funds (FCT/MEC) through Project UID/QUI/50006/2013, co-financed by European Union (FEDER under the Partnership Agreement PT2020); and from Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (project NORTE-01-0145-FEDER 000024). ...

A library of N-phenolic and N-catecholic dehydroamino acid derivatives was prepared using an innovative synthetic strategy that involves mild reaction conditions and simple work-up procedures. The method comprises coupling of phenolic or catecholic acids with β-hydroxyamino acids followed by tert-butyloxycarbonylation of all hydroxyl groups using tert-butyldicarbonate and 4-dimethylaminopyridine as catalyst. Treatment of these amino acids with N,N,N',N'-tetramethylguanidine affords the corresponding O-tert-butyloxycarbonyldehydro-amino acid derivative. Deprotection of the aromatic hydroxyl groups is carried out with trifluoroacetic acid. This synthetic strategy can be applied in a one-pot procedure and yields compounds that can be easily inserted into peptides or other biomolecules after cleavage of the C-protecting group. Preliminary studies of cell viability show that these new compounds display very low or no toxicity. These dehydroamino acids with a phenolic or catecholic moiety can have intrinsic biological activity or used to prepare new hydrogels that mimic mussel adhesive proteins. ; This work received financial support from the Foundation for Science and Technology (FCT, Portugal), through projects UID/QUI/00686/2013, UID/QUI/00686/2016 (CQUM) and UID/QUI/50006/2013-POCI-01-0145-FEDER-007265, co-financed by European Union (FEDER under the Partnership Agreement PT2020), and from Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (project NORTE-010145-FEDER-24). ...