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Marine invasive macroalgae: Turning a real threat into a major opportunity - the biotechnological potential of Sargassum muticum and Asparagopsis armata

Publication . Pinteus, Susete; Lemos, Marco F.L.; Alves, Celso; Neugebauer, Agnieszka; Silva, Joana; Thomas, Olivier P.; Botana, Luis M.; Gaspar, Helena; Pedrosa, Rui

Marine invasive species are widely recognized as one of the worst threats to marine ecosystems integrity, un-balancing native communities, which may lead to paramount ecological and economic impacts. Within invasiveseaweeds, Sargassum muticum and Asparagopsis armata are recognized as successful invaders in Europe andAmerica. Despite several attempts to control the spread of marine invaders, until now, all have proven to beelusive, and therefore, alternative strategies should be embraced.Worldwide, seaweeds have been increasingly explored due to their ability to produce bioactive compounds.However, one of the main problems associated with the production/extraction of these bioactive compounds fornew products development, is the source availability and the potential negative environmental consequences ofthis exploitation.Within this framework, the use of invasive species to obtain natural bioactive compounds presents us with atwo-folded opportunity - high availability of the biological material for the extraction of unique bioactivecompounds for new products development, and through specimen collection, mitigating negative eﬀects causedby alien species, contributing for ecosystem integrity and sustainability.Over the last decades, the brown seaweed S. muticum and the red A. armata have been studied all over theworld for their capacity to produce bioactive compounds, with main results pointing towards their high potentialas producers of antioxidant, antifouling, antimicrobial, and antitumor compounds.The present review summarizes the biotechnological potential of S. muticum and A. armata as producers ofbioactive compounds, while addressing the potential use of global threats as important blue growth pawns.

2018-08-08Journal article

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From marine origin to therapeutics: the antitumor potential of marine algae-derived compounds

Publication . Alves, Celso; Silva, Joana; Pinteus, Susete; Gaspar, Helena; Alpoim, Maria C.; Botana, Luís M.; Pedrosa, Rui

Marine environment has demonstrated to be an interesting source of compounds with uncommon and unique chemical features on which themolecularmodeling and chemical synthesis of new drugs can be based with greater efficacy and specificity for the therapeutics. Cancer is a growing public health threat, and despite the advances in biomedical research and technology, there is an urgent need for the development of new anticancer drugs. In this field, it is estimated that more than 60% of commercially available anticancer drugs are natural biomimetic inspired. Among the marine organisms, algae have revealed to be one of the major sources of new compounds of marine origin, including those exhibiting antitumor and cytotoxic potential. These compounds demonstrated ability to mediate specific inhibitory activities on a number of key cellular processes, including apoptosis pathways, angiogenesis, migration and invasion, in both in vitro and in vivo models, revealing their potential to be used as anticancer drugs. This review will focus on the bioactive molecules from algae with antitumor potential, from their origin to their potential uses, with special emphasis to the alga Sphaerococcus coronopifolius as a producer of cytotoxic compounds.

2018Journal article

Open access

Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells

Publication . Soares, Jorge; Costa, Vera Marisa; Gaspar, Helena; Santos, Susana; Bastos, Maria de Lourdes; Carvalho, Félix; Capela, João Paulo

Synthetic cathinones also known as β-keto amphetamines are a new group of recreational designer drugs. We aimed to evaluate the cytotoxic potential of thirteen cathinones lacking the methylenedioxy ring and establish a putative structure-toxicity profile using differentiated SH-SY5Y cells, as well as to compare their toxicity to that of amphetamine (AMPH) and methamphetamine (METH). Cytotoxicity assays [mitochondrial 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction and lysosomal neutral red (NR) uptake] performed after a 24-h or a 48-h exposure revealed for all tested drugs a concentration-dependent toxicity. The rank order regarding the concentration that promoted 50 % of toxicity, at 24 h exposure, by the MTT assay was: 3,4-dimethylmethcathinone (3,4-DMMC)>METH > mephedrone ≈ α-pyrrolidinopentiophenone > AMPH ≈ methedrone > pentedrone > buphedrone ≈ flephedrone>α-pyrrolidinobutiophenone > methcathinone ≈ N-ethylcathinone>α-pyrrolidinopropiophenone>N,N-dimethylcathinone ≈ amfepramone. Apoptotic cell death signs were seen for all studied cathinones. 3,4-DMMC, methcathinone and pentedrone triggered autophagy activation, as well as increased reactive oxygen species production, and N-acetyl-L-cysteine (NAC) totally prevented that rise. Importantly, NAC was also able to prevent the cytotoxicity promoted by 6 tested drugs, ruling for an involvement of oxidative stress in the toxic events observed. The increased lipophilic chain on the alpha carbon, the presence and the high steric volume occupied by the substituents on the aromatic ring, and the substitution of the pyrrolidine ring by its secondary amine analogue have proved to be key points for the cytotoxicity profile of these cathinones. The structure-toxicity relationship established herein may enlighten future human relevant mechanistic studies, and future clinical approaches on intoxications.

2019Journal article

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Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones

Publication . Gaspar, Helena; Bronze, Soraia; Oliveira, Catarina; Victor, Bruno L.; Machuqueiro, Miguel; Pacheco, Rita; Caldeira, Maria João; Santos, Susana

The emergence of potentially dangerous new psychoactive substances (NPS) imposes enormous challenges on forensic laboratories regarding their rapid and unambiguous identification. Access to comprehensive databases is essential for a quick characterization of these substances, allowing them to be categorized according to national and international legislations. In this work, it is reported the synthesis and structural characterization by NMR and MS of a library encompassing 21 cathinones, 4 of which are not yet reported in the literature, but with structural characteristics that make them a target for clandestine laboratories. This in-house library will be an important tool accessible to forensic laboratories, for the quick identification of seized NPS. The in vitro cytotoxicity of all cathinones was assessed in HepG2 cells, to have a preliminary but effective indication of their human hepatotoxicity potential. The two new cathinones DMB (8) and DMP (9) were the more cytotoxic, followed by the already seized mephedrone (2), 3,4-DMMC (3), 4-MDMC (7), NEB (12) with EC50 values ranging from 0.81 mM for (3) to 1.28 mM for (2). Results suggest an increase of cytotoxicity with the increase of the chain length of the acyl moiety and with the substitution (with one or two methyl groups) in the aromatic ring. The nature of the amine moiety seems to play only a minor role in the cytotoxic effect. Molecular dynamics simulations were performed to evaluate the molecular details related with the observed cytotoxicities. Although these studies indicated that cathinones are able to cross lipid bilayers with relative ease, when in their neutral forms, it was observed only a partial correlation between lipophilicity and cytotoxicity, indicating that membrane trafficking may not be the only key factor influencing the bioactivity of these compounds. This work is a valuable contribution to the forensic science field since a quick identification of novel cathinones is urgent to match their rapid increase in the market.

2018Journal article

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