Pró-fármacos fotoativáveis do péptido AAPV: síntese e avaliação da libertação controlada por luz

Dissertação de mestrado em Bioquímica Aplicada (área de especialização em Biomedicina)

Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-Aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors

The synthesis and biological evaluation of novel 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 3, 4 and 5 as VEGFR-2 tyrosine kinase inhibitors, are reported. The 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 4a-4h, with the arylurea in the meta position to the thioether, showed the lowest IC50 values in enzymatic assays (10-206 nM), the most potent compounds 4d-4h (IC50 10-28 nM) bearing hydrophobic groups (Me, F, CF3 and Cl) in the terminal phenyl ring. A convincing rationalization was achieved for the highest potent compounds 4 as type II VEGFR-2 inhibitors, based on the simultaneous presence of: (1) the thioether linker and (2) the arylurea moiety in the meta position. For compounds 4, significant inhibition of Human Umbilical Vein Endothelial Cells (HUVECs) proliferation (BrdU assay), migration (wound-healing assay) and tube formation were observed at low concentrations. These compounds have also shown to increase apoptosis using the TUNEL assay. Immunostaining for total and phosphorylated (active) VEGFR-2 was performed by Western blotting. The phosphorylation of the receptor was significantly inhibited at 1.0 and 2.5 microM for the most promising compounds. Altogether, these findings point to an antiangiogenic effect in HUVECs.

Estudo e melhoramento de técnica de aparafusamento de um autorrádio

Dissertação de mestrado em Engenharia Mecânica

Acetylated bacterial cellulose coated with urinary bladder matrix as a substrate for retinal pigment epithelium

This work evaluated the effect of acetylated bacterial cellulose (ABC) substrates coated with urinary bladder matrix (UBM) on the behavior of Retinal Pigment Epithelium (RPE), as assessed by cell adhesion, proliferation and development of cell polarity exhibiting transepithelial resistance and polygonal shaped-cells with microvilli. Acetylation of bacterial cellulose (BC) generated a moderate hydrophobic surface (around 65°) while the adsorption of UBM onto these acetylated substrates did not affect significantly the surface hydrophobicity. The ABS substrates coated with UBM enabled the development of a cell phenotype closer to that of native RPE cells. These cells were able to express proteins essential for their cytoskeletal organization and metabolic function (ZO-1 and RPE65), while showing a polygonal shaped morphology with microvilli and a monolayer configuration. The coated ABC substrates were also characterized, exhibiting low swelling effect (between 1.52.0 swelling/mm3), high mechanical strength (2048 MPa) and non-pyrogenicity (2.12 EU/L). Therefore, the ABC substrates coated with UBM exhibit interesting features as potential cell carriers in RPE transplantation that ought to be further explored.

Preparação de suspensões aquosas de nanopartículas de carbono para deposição em superfícies

Dissertação de mestrado integrado em Engenharia de Materiais

Synthesis of iminosugars through diastereo/enantioselective diels-alder cycloaddition

Tese de Doutoramento em Ciências (Especialidade em Química)

Development of folate-targeted liposomes for rheumatoid arthritis therapy

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

Protein-based nanodevices for therapeutic applications

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

Synthesis of new peptide derivatives that self-assemble into nanostructured hydrogels for biomedical applications

Tese de Doutoramento em Ciências (área de especialização em Química)

HOXA9 as a key regulator in glioma initiation, aggressiveness and response to therapy

Tese de Doutoramento em Ciências da Saúde

Morphology and oxygen incorporation effect on antimicrobial activity of silver thin films

Ag and AgxO thin films were deposited by non-reactive and reactive pulsed DC magnetron sputtering, respectively, with the final propose of functionalizing the SS316L substrate with antibacterial properties. The coatings were characterized chemically, physically and structurally. The coatings nanostructure was assessed by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), while the coatings morphology was determined by scanning electron microscopy (SEM). The XRD and XPS analyses suggested that Ag thin film is composed by metallic Ag, which crystallizes in fcc-Ag phase, while the AgxO thin film showed both metallic Ag and Ag-O bonds, which crystalize in fcc-Ag and silver oxide phases. The SEM results revealed that Ag thin film formed a continuous layer, while AgxO layer was composed of islands with hundreds of nanometers surrounded by small nanoparticles with tens of nanometers. The surface wettability and surface tension parameters were determined by contact angle measurements, being found that Ag and AgxO surfaces showed very similar behavior, with all the surfaces showing a hydrophobic character. In order to verify the antibacterial behavior of the coatings, halo inhibition zone tests were realized for Staphylococcus epidermidis and Staphylococcus aureus. Ag coatings did not show antibacterial behavior, contrarily to AgxO coating, which presented antibacterial properties against the studied bacteria. The presence of silver oxide phase along with the development of different morphology were pointed as the main factors in the origin of the antibacterial effect found in AgxO thin film. The present study demonstrated that AgxO coating presented antibacterial behavior and its application in cardiovascular stents is promising.

Biotechnological valorization of waste cooking oils: lipase and microbial lipids production by Yarrowia lipolytica

[Excerpt] Waste cooking oils (WCO) generated from vegetable oils used at high temperatures in food frying, cause environmental problems and must be reutilized. New strategies to valorize these wastes are attracting a great scientific interest due to the important advantages offered from an economic and environmental point of view. A microbial platform can be established to convert low-value hydrophobic substrates, such as waste cooking oils, to microbial lipids (single cell oil, SCO) and other value-added bioproducts, such as lipase. (...)

Cutinase promotes dry esterification of cotton cellulose

Cutinase from Thermobifida fusca was used to esterify the hydroxyl groups of cellulose with the fatty acids from triolein. Cutinase and triolein were pre-adsorbed on cotton and the reaction proceeded in a dry state during 48 hours at 35ºC. The cutinase-catalyzed esterification of the surface of cotton fabric resulted in the linkage of the oleate groups to the glycoside units of cotton cellulose. The superficial modification was confirmed by performing ATR-FTIR on treated cotton samples and by MALDI-TOF analysis of the liquors from the treatment of the esterified cotton with a crude cellulase mixture. Modified cotton fabric also showed a significant increase of hydrophobicity. This work proposes a novel bio-based approach to obtain hydrophobic cotton. This article is protected by copyright. All rights reserved.

Biocatalysis in micellar systems

[Excert] Biocatalysis and biotransformations are environmentally friendly, and allow the development of sustainable production processes on a large scale. Thus, these processes are becoming important alternatives to conventional chemistry in the drug, biochemical, and emerging biorenewable energy industries. Biocatalysts are required to function under non-conventional conditions, such as in organic solvents, being competitive in terms of cost and efficiency. In fact, the technological utility of enzymes can be enhanced greatly by using them in the presence of organic solvents, rather than in their natural aqueous reaction media. Multiphase systems are more complex but offer a new field of possibilities. The presence of hydrophobic solvents in biocatalysis allows the conversion of poorly water soluble substrates more efficiently. The accessibility of hydrophobic substrates to enzymes or whole cells presents an interesting challenge for researchers and technologists. In this context, microemulsions are a promising tool in enzyme technology. This chapter presents an overview of the characterization of biphasic and microemulsion systems and their applications in biotransformation processes (...).

Engineering a commercial cold-adapted xylanase for improved low pH stability

Dissertação de mestrado em Genética Molecular