Daniel de L. Pontes

Comparative Study on the Antioxidant and Anti-Toxoplasma Activities of Vanillin and Its Resorcinarene Derivative

A resorcinarene derivative of vanillin, resvan, was synthesized and characterized by spectroscopic techniques. We measured the cytotoxicity (in vivo and in vitro), antioxidant and anti-Toxoplasma activities of vanillin and the resorcinarene compound. Here we show that vanillin has a dose-dependent behavior with IC50 of 645 µg/mL through an in vitro cytotoxicity assay. However, we could not observe any cytotoxic response at higher concentrations of resvan (IC50 > 2,000 µg/mL). The in vivo acute toxicity assays of vanillin and resvan exhibited a significant safety margin indicated by a lack of systemic and behavioral toxicity up to 300 mg/kg during the first 30 min, 24 h or 14 days after administration. The obtained derivative showed greater antioxidative activity (84.9%) when comparing to vanillin (19.4%) at 1,000 μg/mL. In addition, vanillin presents anti-Toxoplasma activity, while resvan does not show that feature. Our findings suggest that this particular derivative has an efficient antioxidant activity and a negligible cytotoxic effect, making it a potential target for further biological investigations.

Structure and in vitro activities of a Copper II-chelating anionic peptide from the venom of the scorpion Tityus stigmurus

HIGHLIGHTSTanP is anionic peptide rich in aspartic acid.TanP presented chelation potential of copper metal.TanP structure is sensitive to pH variation of the medium.TanP induced macrophage proliferation, though decreasing the release of NO. ABSTRACT Anionic Peptides are molecules rich in aspartic acid (Asp) and/or glutamic acid (Glu) residues in the primary structure. This work presents, for the first time, structural characterization and biological activity assays of an anionic peptide from the venom of the scorpion Tityus stigmurus, named TanP. The three‐dimensional structure of TanP was obtained by computational modeling and refined by molecular dynamic (MD) simulations. Furthermore, we have performed circular dichroism (CD) analysis to predict TanP secondary structure, and UV–vis spectroscopy to evaluate its chelating activity. CD indicated predominance of random coil conformation in aqueous medium, as well as changes in structure depending on pH and temperature. TanP has chelating activity on copper ions, which modified the peptides secondary structure. These results were corroborated by MD data. The molar ratio of binding (TanP:copper) depends on the concentration of peptide: at lower TanP concentration, the molar ratio was 1:5 (TanP:Cu2+), whereas in concentrated TanP solution, the molar ratio was 1:3 (TanP:Cu2+). TanP was not cytotoxic to non‐neoplastic or cancer cell lines, and showed an ability to inhibit the in vitro release of nitric oxide by LPS‐stimulated macrophages. Altogether, the results suggest TanP is a promising peptide for therapeutic application as a chelating agent.

Dextran: Influence of Molecular Weight in Antioxidant Properties and Immunomodulatory Potential.

Dextrans (α-d-glucans) extracted from Leuconostoc mesenteroides, with molecular weights (MW) of 10 (D10), 40 (D40) and 147 (D147) kDa, were evaluated as antioxidant, anticoagulant and immunomodulatory drugs for the first time. None presented anticoagulant activity. As for the antioxidant and immunomodulatory tests, a specific test showed an increase in the dextran activity that was proportional to the increase in molecular weight. In a different assay, however, activity decreased or showed no correlation to the MW. As an example, the reducing power assay showed that D147 was twice as potent as other dextrans. On the other hand, all three samples showed similar activity (50%) when it came to scavenging the OH radical, whereas only the D10 sample showed sharp activity (50%) when it came to scavenging the superoxide ion. D40 was the single dextran that presented with immunomodulatory features since it stimulated the proliferation (~50%) of murine macrophages (RAW 264.7) and decreased the release of nitric oxide (~40%) by the cells, both in the absence and presence of lipopolysaccharides (LPS). In addition, D40 showed a greater scavenging activity (50%) for the hydrogen peroxide, which caused it to also be the more potent dextran when it came to inhibiting lipid peroxidation (70%). These points toward dextrans with a 40 kDa weight as being ideal for antioxidant and immunomodulatory use. However, future studies with the D40 and other similarly 40 kDa dextrans are underway to confirm this hypothesis.

Relation between topology and stability of bent titanocenes

AbstractBent metallocenes are a class of organometallic compounds that are widely used as catalysts in olefin polymerization procedures. We found a linear relation between the relative stability of bent titanocenes and the average delocalization index (DI) for Ti–C (from the cyclopentadienyl ring) atomic pairs within the evaluated compounds. As a consequence, the stability of the bent titanocenes can be estimated from their topologies. However, secondary interactions between the ligands of some of the bent titanocenes reduce the coefficient of determination for the average DI–stability relation. FigureMolecular graph of one of the bent titanocenes studied in this work, and a plot showing the linear relation between the delocalization index (DI) of Ti–C (from the π-ligand) and the stability of the corresponding bent titanocene

A vanillin-based copper(II) metal complex with a DNA-mediated apoptotic activity

Vanillin (vanH) is the major component of vanilla and one of the most widely used flavoring agents. In this work the complex [Cu(phen)(van)2] was prepared and characterized by structural (X-ray), spectroscopic (IR, UV-Vis, EPR) and electrochemical techniques. This compound showed an octahedral geometry with an unusual arrangement of the vanillin ligands, where the methoxy groups of the vanillinate ions are coordinated opposite to each other. The compound promoted DNA cleavage in the presence of glutathione (GSH) and H2O2. At 40 μmol L−1 of complex with GSH (10 mmol L−1), there is a complete cleavage of DNA to nicked form II, while only at 10 μmol L−1 of this complex with H2O2 (1 mmol L−1) an extensive cleavage leading to form III took place. Additionally, we have evidences of superoxide generation upon reaction with GSH. Therefore, DNA fragmentation occurs likely through an oxidative pathway. MTT assays indicated that the complex is highly cytotoxic against three distinct cell lines: B16–F10 (IC50 = 3.39 ± 0.61 μmol L−1), HUH-7 (IC50 = 4.22 ± 0.31 μmol L−1) and 786-0 (IC50 = 10.38 ± 0.91 μmol L−1). Flow cytometry studies conducted with 786-0 cell line indicated cell death might occur by apoptosis. Cell cycle progression evaluated at 5 and 10 μmol L−1 resulted in a clear increase of 786-0 cells at G1 phase and depletion of G2/M, while higher doses showed an expressive increase of sub-G1 phase. Altogether, these results pointed out to a promising biological activity and potential as an anti-cancer agent.

CHROMATOGRAPHIC INVESTIGATION OF RUTHENIUM NITROSYL COMPLEX: NO INTERCONVERSION AND REACTIONS WITH BIOLOGICAL REDUCTANTS

One experimental strategy to prepare a nitrosyl metal complex is based on the acid-base conversion of NO2 into NO. Here, we employed UV-vis absorption and FTIR spectroscopies to investigate the reaction of cis-[Ru(NO2)(bpy)2(imN)]PF6 with H3O, which produced cis-[Ru(NO)(bpy)2(imN)](PF6)3 complex. Chromatographic studies were carried out and showed that immediately after nitrite complex was dissolved only one species was present with retention time(tR) of 6.81 minutes. Addition of H3O to nitrite complex led to the formation of one major peak with tR of 3.92 min supporting nitrosyl complex formation. The reaction of nitrosyl complex with cysteine was also monitored by HPLC and it showed clearly the formation and followed decrease of a peak at 3.38 minute with maximum absorption at 380 nm, consistent with an intermediate complex. Later, it was observed the appearance of a peak at 4.15 minute with absorption band at 470 nm. In contrast to the reaction with cysteine, methionine did not show the formation of any intermediate. The use of HPLC was an important tool to support mechanistic assumptions for nitrosyl reactions.