Síntese e caracterização de derivados da L-fenilalanina e L-tirosina alinhada à “Química Verde” e avaliação da toxicidade / Synthesis and characterization of L-phenylalanine and L-tyrosine derivatives in line with “Green Chemistry” and evaluation of toxicity

A maioria dos fármacos encontrados atualmente na terapêutica moderna são de origem sintética, levando os grupos de pesquisa a estarem constantemente à procura de novos candidatos a fármacos. Sínteses e processos conduzidos com vistas a uma menor agressão ao meio ambiente ganham espaço atualmente em meios acadêmicos e industriais, alinhados aos princípios da “Química Verde”. Este trabalho foi realizado seguindo esse propósito, em que as substâncias N-(L-fenilalaninil)-benzamida (P1) e N-(L-benzoato de tirosinil)-benzamida (P2) foram preparadas através de reações de benzoilação dos aminoácidos de partida L-fenilalanina e L-tirosina, pelo clássico método de Schotten-Baumann, em meio aquoso e temperatura ambiente. Os produtos foram purificados por recristalização e caracterizados por ponto de fusão, cromatografia em camada delgada (CCD) e espectroscopias no ultravioleta-visível (UV-VÍS) e no infravermelho (IV). Foram ainda investigadas as atividades antioxidante qualitativa com o radical difenilpicrilhidrazil (DPPH) e de potencial tóxico frente à larvas de Artemia salina Leach. Apenas P1 indicou significante atividade antioxidante. O teste de toxicidade dos produtos revelou serem atóxicos, de acordo com os valores de concentração letal média (CL50) obtidos. Apesar dos rendimentos baixos obtidos nas reações, as caracterizações sinalizam para o sucesso das sínteses de P1 e P2, numa estratégia sintética econômica, rápida e de baixo impacto ambiental.

Green process in benzoic acid derivatives synthesis/ Processo verde em síntese de derivados de ácido benzoico

Employing a methodology that meets various requirements of "Green Chemistry", the substances quinazolinyl benzoate (P1) and N-4-imidazolphenylbenzamide (P2) were synthesized through benzoylation reactions by the classical Schotten-Baumann method, in an aqueous environment and room temperature. The products were purified by recrystallization and characterized by melting point, thin layer chromatography (TLC) and infrared spectroscopy. Qualitative antioxidant activities with the diphenylpicrylhydrazyl radical (DPPH) and toxic potential against Artemia salina Leach larvae were also investigated. Only P2 indicated significant antioxidant activity. According to the medium lethal concentration values (LC50), used for P1 and P2, the toxic potential revealed, respectively, to be moderate for P1 and weak for P2. Despite the low yield obtained for the synthesis of P1, the characterizations indicate success in the preparations, within a synthetic strategy of low cost, efficient and ecologically sustainable

Avaliações fitoquímica, fitotóxica e antifúngica da entrecasca do caule de Pterodon pubescens Benth (sucupira branca) / Phytochemical, phytothoxic and antifungal evaluations of stem bark of Pterodon pubescens Benth (sucupira branca)

Estudos químico-farmacológicos visando a obtenção de novos fármacos a partir de produtos vegetais são de grande importância na indústria. Este trabalho relata pela primeira vez a análise fitoquímica em meio hidrofílico e lipofílico para detecção de metabólitos secundários presentes no extrato bruto da entrecasca do caule de Pterodon pubescens Benth (sucupira branca), uma planta típica do Cerrado, bem como as avaliações do potencial antifúngico e tóxico do extrato bruto da entrecasca e de quatro frações obtidas a partir do extrato bruto por partição líquido-líquido com solventes de diferentes polaridades, ainda não descritos na literatura. Os resultados da análise fitoquímica foram realizados seguindo-se procedimento da literatura, informando dados positivos a uma série de metabólitos secundários, com destaque àqueles com potencial antioxidante. O extrato hidrofílico apresentou um maior número de resultados positivos para os metabólitos estudados. A investigação do potencial tóxico, tanto do extrato bruto como das quatro frações semipuras frente às larvas de Artemia salina Leach indicou valores de CL50 que comparado a dados da literatura situaram-se nas faixas de moderadamente a fracamente tóxicos. A avaliação da atividade antifúngica revelou que os extratos particionados hexano e acetato de etila são sensíveis à inibição de Candida albicans, comparado com padrão positivo, enquanto o extrato bruto lipofílico e as frações clorofórmio e 1-butanol apresentam maior atividade de inibição. Os estudos realizados sinalizam que o extrato bruto hidroetanólico da entrecasca do caule de P. pubescens contém substâncias que possam conferir propriedades medicinais, além do uso seguro para fins terapêuticos

DESENVOLVIMENTO DE ALFACE LISA E CRESPA EM SISTEMA HIDROPÔNICO VERTICAL

A agricultura está em busca do incremento de produtividade nos seus mais distintossegmentos. Na hidroponia o cultivo verticalizado traz a possibilidade de se alcançartal resultado. Este trabalho teve como objetivo avaliar um sistema de cultivo verticaldesenvolvido com canos de PVC, dentro de ambiente protegido, com a comparaçãoentre dois tipos de alface (crespa e lisa) em dois suportes de enraizamento, argilaexpandida e sombrite. O delineamento experimental utilizado foi inteiramentecasualizado, esquema fatorial 2x2, com três repetições. Com base nas plantasanalisadas não houve diferença estatística, entre os suportes de enraizamento,porém a alface lisa apresentou número de folhas e menor comprimento do caule

Loss of DOCK2 potentiates Inflammatory Bowel Disease–associated colorectal cancer via immune dysfunction and IFNγ induction of IDO1 expression

Inflammatory Bowel Disease-associated colorectal cancer (IBD-CRC) is a known and serious complication of Inflammatory Bowel Disease (IBD) affecting the colon. However, relatively little is known about the pathogenesis of IBD-associated colorectal cancer in comparison with its sporadic cancer counterpart. Here, we investigated the function of Dock2, a gene mutated in ~10% of IBD-associated colorectal cancers that encodes a guanine nucleotide exchange factor (GEF). Using a genetically engineered mouse model of IBD-CRC, we found that whole body loss of Dock2 increases tumourigenesis via immune dysregulation. Dock2-deficient tumours displayed increased levels of IFNγ-associated genes, including the tryptophan metabolising, immune modulatory enzyme,IDO1, when compared to Dock2-proficient tumours. This phenotype was driven by increased IFNγ-production in T cell populations, which infiltrated Dock2-deficient tumours, promoting IDO1 expression in tumour epithelial cells. We show that IDO1 inhibition delays tumourigenesis in Dock2 knockout mice, and we confirm that this pathway is conserved across species as IDO1 expression iselevated in human IBD-CRC and in sporadic CRC cases with mutated DOCK2. Together, these data demonstrate a previously unidentified tumour suppressive role of DOCK2 that limits IFNγ-induced IDO1 expression and cancer progression, opening potential new avenues for therapeutic intervention

Reversal of mitochondrial malate dehydrogenase 2 enables anaplerosis via redox rescue in respiration-deficient cells

Inhibition of the electron transport chain (ETC) prevents the regeneration of mitochondrial NAD+, resulting in cessation of the oxidative tricarboxylic acid (TCA) cycle and a consequent dependence upon reductive carboxylation for aspartate synthesis. NAD+ regeneration alone in the cytosol can rescue the viability of ETC-deficient cells. Yet, how this occurs and whether transfer of oxidative equivalents to the mitochondrion is required remain unknown. Here, we show that inhibition of the ETC drives reversal of the mitochondrial aspartate transaminase (GOT2) as well as malate and succinate dehydrogenases (MDH2 and SDH) to transfer oxidative NAD+ equivalents into the mitochondrion. This supports the NAD+-dependent activity of the mitochondrial glutamate dehydrogenase (GDH) and thereby enables anaplerosis—the entry of glutamine-derived carbon into the TCA cycle and connected biosynthetic pathways. Thus, under impaired ETC function, the cytosolic redox state is communicated into the mitochondrion and acts as a rheostat to support GDH activity and cell viability.P.A.-M was supported by a Marie Skłodowska-Curie Actions individual fellowship and the Beug Foundation. A.V. was supported by Fonds Wetenschappelijk Onderzoek (FWO Vlaanderen). J.E.-H. was supported by an MRC studentship. J.C.A was supported by a Cancer Research UK Career Development Fellowship (C47559/A16243). S.-M.F. acknowledges funding from the European Research Council under the ERC Consolidator grant agreement no. 771486–MetaRegulation, FWO Projects, Fonds Baillet Latour, KU Leuven-FTBO/Internal Funding, Stichting Tegen Kanker and the King Baudouin Foundation. Work in the A.J.F. group was supported by a Wellcome Trust-ISSF grant, funding from Barts Charity (MGU0404), and by a Cancer Research UK Centre Grant to Barts Cancer Institute (C355/A25137). The illustrations in the graphical abstract and Figure 5F were created using BioRender.com

ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma

Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic and transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that, in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-coenzyme A (CoA) synthetase 2 (ACSS2) in the nucleus to couple high glucose metabolic flux with acetyl-histone H3 modification of neural crest (NC) lineage and glucose metabolism genes. Importantly, we show that acetaldehyde is a metabolite source for acetyl-histone H3 modification in an ALDH1A3-dependent manner, providing a physiologic function for this highly volatile and toxic metabolite. In a zebrafish melanoma residual disease model, an ALDH1-high subpopulation emerges following BRAF inhibitor treatment, and targeting these with an ALDH1 suicide inhibitor, nifuroxazide, delays or prevents BRAF inhibitor drug-resistant relapse. Our work reveals that the ALDH1A3-ACSS2 couple directly coordinates nuclear acetaldehyde-acetyl-CoA metabolism with specific chromatin-based gene regulation and represents a potential therapeutic vulnerability in melanoma.</p

Niobium and niobium-iron coatings on API 5LX 70 steel applied with HVOF

The present study aimed to create and characterize niobium and niobium-iron60% coatings applied to steel API 5L X70 using the hypersonic thermal spray process (HVOF). The morphologies of the coatings were analyzed using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and profilometry, while the coatings’ hardnesses was evaluated using the Vickers hardness test. The coatings’ corrosion resistance was evaluated by monitoring their open circuit potential and potentiodynamic polarization and performing electrochemical impedance spectroscopy in a 0.05 M NaCl solution. The results showed that the niobium-iron coating contained minor porosity regions, while such defects occurred over large regions of the niobium coating. In terms of corrosion resistance, the coatings obtained in this work promoted a reduction in the substrate’s corrosion rate, but the presence of discontinuities such as porosity compromised the barrier effects of these coatings

Phytochemical Screening and comparison of DPPH radical scavenging from different samples of coffee and Yerba Mate beverages

Abstract- A phytochemical screening of commercial samples of roasted coffee, soluble coffee and yerba maté prepared as tereré and chimarrão consumed in South America was evaluated. All samples were subjected to a qualitative assay for phytochemical screening in order to detect classes of phenolic compounds, as well as FT-IR analysis of the dried crude extracts, Antioxidant potential was conducted with DPPH assay. The results were similar to each sort of samples according to the presence of phenolic compounds classes, meanwhile the antioxidant potential percentage were varied. Index Terms- Ilex paraguariensis, Coffee, Phytochemical screening, Antioxidant potentia