Synthesis of Tetracyclic systems and (Thio)Ureas from Aminodi(Hetero)Arylamines in the Thieno[3,2-b]Pyridine series

Foundation for the Science and Technology (FCT–Portugal) for financial support through the Portuguese NMR network (Bruker 400 Avance III-Univ Minho). FCT and FEDER (European Fund for Regional Development)-COMPETE/QREN/EU for financial support through the research centre PEst-C/QUI/UI686/2011, the research project PTDC/QUI-QUI/111060/2009 and the post-doctoral grant of R.C.C. SFRH/BPD/68344/2010

Riscos microbiológicos dos produtos de origem vegetal

Nos últimos .anos os consumidores estão mais preocupados com a sua saúde quanto à escolha dos seus alimentos. Os vegetais são amplamente recomendados como parte da alimentação diária pelo seu apreciável conteúdo em vitaminas, sais minerais e fibras alimentares. Tem crescido o interesse, principalmente, per aqueles que apresentam na sua composição substâncias com actividade antioxidante, como os carotenóides, a vitamina C e os flavonóides, que os caracterizam como alimentos funcionais

Toxicity effects of fungicide residues on the wine-producing process

We report the detection of several fungicide residues (Dichlofluanid, Benomyl, Iprodione, Procymidone and Vinclozolin) in red and white bottled wines from two Portuguese wine-producing zones. Studies were done in order to evaluate the active compound transfer percentage from grapes to the final product along fermentation process. We also investigated their effects in Saccharomyces and non-Saccharomyces yeasts as well as their influence on the physical, chemical and organoleptic wine properties. All the tested fungicides had a negative effect on in vitro yeast growth, with Dichlofluanid and Benomyl being the most toxic. Zygosaccharomyces rouxii and Saccharomyces cerevisiae were the most resistant yeasts while Rhodotorula glutinis was the most susceptible. Microvinification experiments carried out in the presence of fungicides produced wine samples with unaltered physical, chemical and organoleptic properties, though Benomyl, a slight delay in the initiation of fermentation process was observed

Mathematical models of cytotoxic effects in endpoint tumor cell line assays: Critical assessment of the application of a single parametric value as a standard criterion to quantify the dose-response effects and new unexplored proposal formats

The development of convenient tools for describing and quantifying the effects of standard and novel therapeutic agents is essential for the research community, to perform more precise evaluations. Although mathematical models and quantification criteria have been exchanged in the last decade between different fields of study, there are relevant methodologies that lack proper mathematical descriptions and standard criteria to quantify their responses. Therefore, part of the relevant information that can be drawn from the experimental results obtained and the quantification of its statistical reliability are lost. Despite its relevance, there is not a standard form for the in vitro endpoint tumor cell lines' assays (TCLA) that enables the evaluation of the cytotoxic dose-response effects of anti-tumor drugs. The analysis of all the specific problems associated with the diverse nature of the available TCLA used is unfeasible. However, since most TCLA share the main objectives and similar operative requirements, we have chosen the sulforhodamine B (SRB) colorimetric assay for cytotoxicity screening of tumor cell lines as an experimental case study. In this work, the common biological and practical non-linear dose-response mathematical models are tested against experimental data and, following several statistical analyses, the model based on the Weibull distribution was confirmed as the convenient approximation to test the cytotoxic effectiveness of anti-tumor compounds. Then, the advantages and disadvantages of all the different parametric criteria derived from the model, which enable the quantification of the dose-response drug-effects, are extensively discussed. Therefore, model and standard criteria for easily performing the comparisons between different compounds are established. The advantages include a simple application, provision of parametric estimations that characterize the response as standard criteria, economization of experimental effort and enabling rigorous comparisons among the effects of different compounds and experimental approaches. In all experimental data fitted, the calculated parameters were always statistically significant, the equations proved to be consistent and the correlation coefficient of determination was, in most of the cases, higher than 0.98.The authors are grateful to the Foundation for Science and Technology (FCT) of Portugal and FEDER for financial support to CIMO (UID/AGR/00690/2013); and to the Xunta de Galicia for financial support for the post-doctoral research of M. A. Prieto.info:eu-repo/semantics/publishedVersio

Aminosquaraines as potential photodynamic agents: Synthesis and evaluation of in vitro cytotoxicity

© 2017 Elsevier Ltd The synthesis of several aminosquaraine cationic dyes displaying strong absorption within the so-called phototherapeutic window (650–850 nm) is described. Their cytotoxicity, under dark and illuminated conditions, was tested against several human tumor cell lines (breast, lung, cervical and hepatocellular carcinomas) and non-tumor porcine liver primary cells. All compounds showed to inhibit the growth of the tumor cells upon irradiation more than in the absence of light, in more or less extension, clearly exhibiting photodynamic activity. The photosensitizing ability against some cell lines, together with the low toxicity for the non-tumor primary PLP2 cells displayed by some of the compounds synthetized, turns them into potential candidates as photosensitizers for PDT.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) and FEDER for CIMO (UID/AGR/00690/2013) and CQ-VR (UID/QUI/00616/2013) financial support.info:eu-repo/semantics/publishedVersio

Radical scavenging activity, lipid peroxidation inhibition and redox profile of aminodiarylamines in the thieno[3,2-b]pyridine series

The reducing properties of diarylamines make them very important as antioxidants, especially as radical scavengers as it has been demonstrated by our and other research groups [1 -3]. Three di(hetero)arylamines were prepared by C- N coupling of the methyl3-amino-6-bromothieno(3,2- b]pyridine-2-carboxylate with bromonitrobenzenes and further reduced to the amino compounds 1a-c (Scheme) (4].FCT for financial support through the NMR Portuguese network (Bruker 400 Avance 111-Univ Minho). To FCT and FEDER-COMPETE/QREN/EU for financial support through the research unities PEstC/ QUI/UI686/2011 and PEst-OE/AGR/UI0690/2011 , the research project PTDC/QUI-QUI/111 060/2009 and the post-Doctoral grant attributed to R.C.C. (SFRH/SPD/68344/201 0) also financed by POPH and FSE

The Role of Gut Microbiota in the Etiopathogenesis of Multiple Chronic Diseases

Chronic diseases (CD) may result from a combination of genetic factors, lifestyle and social behaviours, healthcare system influences, community factors, and environmental determinants of health. These risk factors frequently coexist and interact with one another. Ongoing research and a focus on personalized interventions are pivotal strategies for preventing and managing chronic disease outcomes. A wealth of literature suggests the potential involvement of gut microbiota in influencing host metabolism, thereby impacting various risk factors associated with chronic diseases. Dysbiosis, the perturbation of the composition and activity of the gut microbiota, is crucial in the etiopathogenesis of multiple CD. Recent studies indicate that specific microorganism-derived metabolites, including trimethylamine N-oxide, lipopolysaccharide and uremic toxins, contribute to subclinical inflammatory processes implicated in CD. Various factors, including diet, lifestyle, and medications, can alter the taxonomic species or abundance of gut microbiota. Researchers are currently dedicating efforts to understanding how the natural progression of microbiome development in humans affects health outcomes. Simultaneously, there is a focus on enhancing the understanding of microbiome-host molecular interactions. These endeavours ultimately aim to devise practical approaches for rehabilitating dysregulated human microbial ecosystems, intending to restore health and prevent diseases. This review investigates how the gut microbiome contributes to CD and explains ways to modulate it for managing or preventing chronic conditions.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support by national funds FCT/MCTES CIMO (UIDB/00690/2020 and UIDP/00690/2020) and SusTEC (LA/P/0007/2020); national funding by FCT, P.I., through the institutional scientific employment program-contract for S.Heleno and R. Calhelha contracts.info:eu-repo/semantics/publishedVersio

Bioactive properties of pollen samples collected in the Northeast of Portugal

Reactive oxygen species are formed during normal cellular metabolism, but when present in high concentration they become toxic. Mammalian ce lls possess intracellular defences such as superoxide dismutase, catalase or glutathione peroxidase in order to protect the cells against excessive levels of free radicals

Chemical characterization and bioactive properties of bee venom samples from Northeast of Portugal

O veneno de abelha (VA) ou apitoxina é um produto apícola que tem sido utilizado desde os tempos ancestrais para múltiplas finalidades, nomeadamente em medicina tradicional na apiterapia. Trata -se de uma mistura complexa de substâncias que lhe conferem propriedades bioativas. No presente trabalho, analisaram -se cinco amostras de VA obtidas a partir de Apis mellifera iberiensis de dois apiários diferentes (Aveleda e Milhão, na região de Bragança). Foram, caracterizadas quimicamente e avaliadas quanto às suas propriedades antioxidantes, anti -inflamatórias e citotóxicas. A análise das amostras por LC -DAD -ESI/MSn demonstrou que a melitina (MEL) era o composto maioritário, seguido da fosfolipase A2 (PLA2) e da apamina (APA). Todas as amostras demonstraram atividade antioxidante, medida pela capacidade captadora de radicais livres, poder redutor e inibição da peroxidação lipídica, e anti -inflamatória, determinada pela capacidade de diminuir a formação de NO em macrófagos de rato (RAW 264,7). No entanto, não foi observada uma relação direta entre as propriedades bioativas mencionadas e o perfil químico (qualitativo ou quantitativo) das amostras. Os resultados obtidos evidenciam, sim, que existem concentrações específicas, nas quais estes compostos são mais ativos (e.g., presentes na única amostra obtida no apiário de Aveleda). As amostras de VA demonstraram também propriedades citototóxicas semelhantes para todas as linhas celulares tumorais testadas (MCF -7, NCI -H460, HeLa e HepG2), sendo as linhas MCF -7 (carcinoma de mama) e HeLa (carcinoma cervical) as mais suscetíveis. Apesar disso, as amostras estudadas parecem não ser adequadas para o tratamento de carcinoma de mama, hepatocelular e cervical porque, nas concentrações ativas, as amostras também foram tóxicas para células não tumorais (cultura primária de células de fígado de porco, PLP2). Relativamente ao carcinoma do pulmão, o VA deve ser utilizado abaixo da concentração tóxica para as células não tumorais. Em geral, o presente estudo evidenciou o enorme potencial bioativo do VA, sendo o primeiro trabalho realizado com amostras Portuguesas.Bee venom (BV) or apitoxin is an apiculture product that has been used since ancient times for several applications namely in the traditional medicine apitherapy. It is a complex mixture of substances responsible for different bioactive properties. In the present work, five bee venom samples obtained from Apis mellifera iberiensis from two different apiaries in Bragança (Aveleda and Milhão) were chemically characterized and evaluated for their antioxidant, anti -inflammatory and cytotoxic properties. The LC/DAD/ESI -MSn analysis of the samples showed that melittin was the most abundant compound, followed by phospholipase A2 and apamin. All the samples revealed antioxidant activity, measured by the free radicals scavenging activity, reducing power and lipid peroxidation inhibition, and anti -inflammatory activity, determined by the capacity to inhibit NO formation in murine macrophages (RAW 264,7). However, it was not observed a direct relation between the mentioned bioactive properties and the chemical profile (qualitative or quantitative) of the samples. The results highlight that there are specific concentrations in which these compounds are more active (e.g., in the single sample obtained from Aveleda apiary). The BV samples also showed similar cytotoxicity for all the tested tumor cell lines (MCF -7, NCI -H460, HeLa and HepG2), being MCF -7 (breast carcinoma) and HeLa (cervical carcinoma) the most susceptible ones. Nevertheless, the studied samples seem to be not suitable to treat breast, hepatocellular and cervical carcinoma because at the active concentrations, the samples were also toxic for non -tumor cells (porcine liver primary culture, PLP2). Regarding the non -small lung cell carcinoma, BV should be used under the concentration toxic for non -tumor cells. Overall, the present study corroborates the enormous bioactive potential of BV being the first report on samples from Portugal.À Fundação para a Ciência e Tecnologia (FCT, Portugal) pelo suporte financeiro ao CIMOinfo:eu-repo/semantics/publishedVersio