Navegando por Palavras-chave "Atividade Biológica"

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    Estudo de estrutura-atividade do peptídeo antimicrobiano IsCT1
    (Universidade Federal de São Paulo (UNIFESP), 2020-04-30) Oliveira, Cyntia Silva De [UNIFESP]; Oliveira Junior, Vani Xavier De [UNIFESP]; Universidade Federal de São Paulo
    Introduction: The increase in multidrug-resistant bacteria represents a major global health challenge, in this scenario, antimicrobial peptides represents a promising alternative for the development of new drugs due to the broad spectrum or good selectivity. Among them, IsCT1 (ILGKIWEGIKSLF-NH2) obtained from the venom of the scorpion Opisthacanthus madagascariensis, has a potent antimicrobial activity, but high hemolytic activity in human erythrocytes. Objectives: To obtain peptides based on the general structure of IsCT1 with point substitutions of amino acid residues on the hydrophilic, hydrophobic or both faces, in order to verify how these changes and their consequent physicochemical changes reflect on the structure and biological activity. Methodology: The peptides were synthesized in solid phase by the Fmoc strategy, purified by liquid chromatography (HPLC), characterized by mass spectrometry (LCESI/MS). Conformational studies were carried out by circular dichroism (CD) in water and solutions of PBS, SDS, TFE. Hemolytic activity assays were performed using human erythrocytes and the antimicrobial activity was tested against strains of Grampositive and Gram-negative bacteria. Anticancer activity was tested in human breast cancer cells / MCF-7A, and cytotoxicity in human breast epithelial cells / MCF-10A. Results and discussion: The analogs showed a reduction in hemolytic activity, mainly when made substitution of the glutamic acid residue present in position 8 of the IsCT1 peptide, this analogs also showed antimicrobial activity in low concentrations and high therapeutic indexes, except for the analogue An5, which had its load increased to +6 by the insertion of three lysine residues in addition to proline in position 8, its showed a reduction in antimicrobial activity and high hemolytic activity. In turn, An2 showed the best results of antimicrobial activity and absence of hemolytic activity up to the concentration of 128 μmol L-1 . It was also observed the activity against human breast cancer cells presented by IsCT1 and by two of the analogs synthesized with substitution in position 7, adding the proline residue (An2 and An8). A direct relationship between secondary structure and biological activity has not been established, since the analogs showed little tendency to form helix in TFE and varying values in SDS. The peptides were also tested for stability against enzymatic degradation, where an increase in resistance was observed, promoted by the insertion of proline in position 8 and a reduction in resistance, when proline was inserted in position 7. Conclusion: The results obtained show how the modifications of amino acid residues along the peptide sequence promote physical-chemical changes capable of interfering both in biological activity and in peptide stability.
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    Nanopartículas superparamagnéticas de óxido de ferro incorporadas em sílica mesoporosa ordenada SBA-15 com potencial aplicação biomédica
    (Universidade Federal de São Paulo (UNIFESP), 2020-03-23) Losito, Danilo Waismann [UNIFESP]; Martins, Tereza da Silva [UNIFESP]; Universidade Federal de São Paulo
    Iron oxide superparamagnetic nanoparticles (SPION) due to their intrinsic properties, as a single magnetic domain, are very promising for biomedical applications, both in diagnosis and therapy. However, their efficiency decreases due to agglomeration and its incorporation in ordered mesoporous silica, such as SBA-15, which has unique properties, such as high surface area (above 800 m2 g -1 ), mesoporous size around 8 nm, with narrow pore size distribution, can, besides to avoid SPION agglomeration, favor magnetically guided drug delivery system. Particle morphology, including size and shape, of SBA-15 may also favor the interaction between SPIONs and silica and in this context, the objective of this work was to prepare and characterize SBA-15 nanocomposites, with different morphologies, and SPIONs prepared by coprecipitation methods and thermo-composition, aiming at application in the biomedical area, as drug carriers, guided by magnetization. The SPIONs (10 and 30 wt%) were incorporated into the SBA-15 with different morphologies by wet impregnation in toluene and the composites formed were characterized by several physical-chemical techniques. The X-ray diffractometry (XRD) and low-angle X-ray scattering (SAXS) data of the composites showed that the crystalline (magnetite) phase of the SPIONs and the SBA-15 mesoporous structure did not undergo significant changes, when compared to pure materials. However, the data obtained from nitrogen physisorption showed significant changes in the textural properties of composites in relation to pure SBA-15, such as the decrease in the volume of adsorbed nitrogen and specific surface area, indicating the incorporation of SPIONs into the mesoporosity of SBA-15, mainly in composites prepared with nanoparticles obtained by thermal decomposition, which is probably a consequence of the smaller size of these nanoparticles. The presence of SPIONs in the mesoporosity and macroporosity of SBA-15 was observed in the images obtained by scanning electron microscopy (SEM) and transmission (TEM), and through dispersive energy spectroscopy (EDS). EDS and thermogravimetry (TG) data showed that the SPIONs content in the composites was lower than the nominal (10 and 30 wt%) due to the presence of oleic acid that was used in the synthesis of the nanoparticles, confirmed by Fourier transform infrared (FTIR) spectroscopy. SEM images showed a rod-like shape for SBA-15 particles with a uniform rod length, this morphology does not affect by the SPIONs incorporation. Magnetic curves profile of the composites also did not change in relation to the profile observed for pure SPIONs. However, the magnetization of the composites was lower due to weight percentage of SPIONs (10 and 30 wt%) in the composites, but with an increase in the magnetization for the composites obtained with the nanoparticles obtained by thermo-decomposition. Analysis of local structure by function of distribution of pairs (PDF) showed that the increase in SPION content in the composites and the reduction in the particle size of the SBA-15 cause significant changes in the local ordering. Toxicity tests have shown that both SPIONs and silicas, as well as composites, are safe for biological applications.