Francielle Pelegrin Garcia

Curcumin-loaded dual pH- and thermo-responsive magnetic microcarriers based on pectin maleate for drug delivery

Magnetic microgels with pH- and thermo-responsive properties were developed from the pectin maleate, N-isopropyl acrylamide, and Fe3O4 nanoparticles. The hybrid materials were characterized by infrared spectroscopy, scanning electron microscope coupled with X-ray energy dispersive spectroscopy, wide angle X-ray scattering, Zeta potential, and magnetization hysteresis measurements. Curcumin (CUR) was loaded into the microgels, and release assays were carried out in simulated environments (SGF and SIF) at different conditions of temperature (25 or 37°C). A slow and sustainability CUR release was achieved under external magnetic field influence. Loaded CUR displayed stability, bioavailability and greater solubility regarding free CUR. Besides, the cytotoxicity assays showed that magnetic microgels without CUR could suppress the Caco-2 cells growth. So, the pectin maleate, N-isopropyl acrylamide, and Fe3O4 could be tailored to elicit hybrid-based materials with satisfactory application in the medical arena.

Unsymmetrical 1,5-diaryl-3-oxo-1,4-pentadienyls and their evaluation as antiparasitic agents.

In this work the synthesis and antiparasitical activity of new 1,5-diaryl-3-oxo-1,4-pentadienyl derivatives are described. First, compounds 1a, 1b, 1c and 1d were prepared by acid-catalyzed aldol reaction between 2-butanone and benzaldehyde, anisaldehyde, p-N,N-dimethylaminobenzaldehyde and p-nitrobenzaldehyde. Reacting each of the methyl ketones 1a, 1b, 1c and 1d with the p-substituted benzaldehydes under basic-catalyzed aldol reaction, we further prepared compounds 2a-2p. All twenty compounds were evaluated for antiproliferative activity, particularly for promastigote of Leishmania amazonensis and epimastigote of Trypanosoma cruzi. All compounds showed good activity while nitro compounds 2i and 2k showed inhibition activity at a few μM.

Controlling cell growth with tailorable 2D nanoholes arrays

A facile and reproducible route that can lead to two-dimensional arrays of nanopores in thin polymer films is demonstrated. The formation of the pores in the polymer films involves breath figure phenomenon and occurs during the film deposition by spin coating. The formation of nanoporous thin films takes only few seconds, and the method does not require complex equipment or expensive chemicals. This method also constitutes a straightforward approach to control the size of the pores formed in thin films. Besides allowing control over the average pore size of the porous films, the use of dynamic deposition with the breath figure phenomenon causes the reduction in the pore size to nanometer scale. The nanoporous arrays obtained by the breath figure are applied as substrates for cell growth, and the effect of their nanopore size on cell growth was evaluated. Notably, it is found that cell viability is related to pore size, where 2D nanoporous structure is more beneficial for cell culture than 2D microporous structures. The change in the average pore size of the polymer films from 1.22 μm to 346 nm results in a threefold increase in cell viability.

The utilization of crisp code in hybrid reactor studies

One of the main applications of the Hybrid Reactors (ADS - Accelerator Driven System) is the incineration of transuranics (TRU) by fast neutrons that emerge from a spallation source in a sub critical reactor waste burner [1, 2]. For this application, an accurate description and prediction of spallation reaction is necessary, including all the characteristics concerning spatial and energetic angular distributions, spallation products and neutron multiplicity. To describe the nuclear reactions at intermediate and high energies, Monte Carlo calculations have been used. The CRISP package considers the intranuclear cascade (INC) that occurs during the spallation process in a realistic time-sequence approach in which all particles inside the nucleus can participate in the cascade and the nuclear density fluctuations are naturally taken into account during the process. The occupation number of each single particle level is considered as a function of time and a more realistic Pauli blocking mechanism can be performed. None of the existing models have effectively used all those features. The evaporation of protons and alpha particles are taken into account making possible the correct prediction of fissilities of actinides and pre-actinides [3]. Another implementation is the NN single-pion production reaction. This reaction is especially relevant if one is interested in neutron or proton multiplicities, since the creation/emission of pions is directly related with the excitation energy of the residual nucleus. We will present some results obtained with the CRISP package for proton-nucleus reaction at intermediate and high energies. This package was obtained by the coupling of the MCMC [4] and MCEF [5] codes, with the introduction of some improvements, such as better Pauli blocking mechanism, which constrains the residual nucleus energetic evolution to the Pauli Principle from the ground-state to the final compound-nucleus formed at the end of the intranuclear cascade process, and introduction of the most relevant resonant excitation and the NN single pion production channel. The results of interest for ADS development are consistent with the experimental data at different proton energies. More detailed calculations are being performed for studying other features of proton-nucleus reactions and with different targets.

Copper and Manganese Cations Alter Secondary Metabolism in the Fungus Penicillium brasilianum

The fungus Penicillium brasilianum LaBioMMi 136 was isolated as an endophyte from Melia azedarach and has shown to be a prominent producer of great diversity of secondary metabolites, although it does not express some biosynthetic routes to other natural compounds found in Penicillium genera. The present study aimed at the diversification of P. brasilianum secondary metabolism by varying the chemical composition used for its growth. Medium composition supplemented with CuSO4 and MnSO4 locked verruculogen biosynthesis and addressed proline to the production of a series of cyclodepsipeptides identified as JBIR 113, JBIR 114 and JBIR 115, never described for this species so far. The induced cyclodepsipeptide JBIR 113 was isolated by the use of combined chromatographic procedures and identified by spectroscopic methods. The unique structure with three neighboring cyclic amino acids proline and twice pipecolinic acid is rare as natural products and has been described for the first time in terrestrial organism. Verruculogen and JBIR 113 exhibited weak antiparasitary activity against Leishmania amazonensis.

Spallation Product Distributions and Neutron Multiplicities for Accelerator-Driven System Using the CRISP Code

Abstract Neutron multiplicities for several targets and spallation products of proton-induced reactions in thin targets of interest to an accelerator-driven system obtained with the CRISP code have been reported. This code is a Monte Carlo calculation that simulates the intranuclear cascade and evaporation/fission competition processes. Results are compared with experimental data, and agreement between each other can be considered quite satisfactory in a very broad energy range of incitant particles and different targets.

Curvulin and spirostaphylotrichins R and U from extracts produced by two endophytic Bipolaris sp. associated to aquatic macrophytes with antileishmanial activity

Abstract In the present study, biological activity and chemical composition of two crude extracts of endophytic fungal strains of Bipolaris genera isolated from two species of aquatic macrophytes: Eichhornia azurea (Kunth) and Eichhornia crassipes (Mart.) were investigated. The nuclear magnetic resonance and mass spectrometry data provided the identification of three main compounds: curvulin (1), spirostaphylotrichin R (2) and U (3). The fragmentation mechanism of the precursor ions towards collision induced dissociation (CID) tandem mass spectrometry experiment (MS/MS) is also proposed. Furthermore, biological screening of the crude extracts displayed antileishmanial activity with IC50 values ranging from 70–84.2 μg.mL−1.

A3K2A3-induced apoptotic cell death of Leishmania amazonensis occurs through caspase- and ATP-dependent mitochondrial dysfunction

Leishmaniasis is a neglected tropical disease that affects millions of people worldwide. Current therapies mainly rely on antimonial drugs that are inadequate because of their high toxicity and increased drug resistance. An urgent need exists to discover new, more effective, more affordable, and more target-specific drugs. Pathways that are associated with apoptosis-like cell death have been identified in unicellular eukaryotes, including protozoan parasites. In the present study, we studied the mechanism of cell death that is induced by A3K2A3 against L. amazonensis. A3K2A3 is a dibenzylideneacetone that has an acyclic dienone that is attached to aryl groups in both β-positions, which is similar to curcuminoids and chalcone structures. This compound was previously shown to be safe with regard to cytotoxicity and active against the parasite. Biochemical and morphological approaches were used in the present study. The results suggested that A3K2A3 caused mitochondrial dysfunction in L. amazonensis promastigotes, leading to mechanisms of cell death that share some common phenotypic features with metazoan apoptosis, such as an increase in reactive oxygen species production, a decrease in the adenosine triphosphate ratio, phosphatidylserine exposure, a decrease in cell volume, caspase production, and DNA fragmentation. Altogether, these findings indicate that apoptosis can indeed be triggered by chemotherapeutic agents.

The CRISP Code for Nuclear Reactions

The CRISP package performs the intranuclear cascade process and the evaporation/fission competition resulting in a code that represents a good tool to describe complexes characteristics of the nuclear reactions, and opens the opportunity for applications in different fields, such as medical physics, photonuclear reactions, spallation or fission process initiated by different probes and in Accelerator Driven Systems, where precise description of energetic and angular neutron distribution, neutron multiplicity and spallation products information are needed. In the CRISP model, was included the time‐sequence characteristics of the MCMC code and the evaporation/fission competition process model of the MCEF. Also, includes improvements in the code, as the excitation of nucleonic resonances heavier than Delta; the initial nuclear ground state construction according to the Fermi model and Pauli principle; and a more realistic Pauli blocking mechanism. Some consequences of the improvements performed in the code w...

Crispoic acid, a new compound from Laelia marginata (Orchidaceae), and biological evaluations against parasites, human cancer cell lines and Zika virus

Abstract The phytochemical study of Laelia marginata (Lindl.) L. O. Williams (Orchidaceae) led to the isolation of a new natural product named crispoic acid (1), together with six other known compounds (2–7). The new natural product was identified as a dimer of eucomic acid and was structurally characterised based upon 1D and 2D NMR and HRMS data. Biological assays with plant crude extract, fractions and isolated compounds were performed against two human cancer cell lines (Hela and Siha), and the tropical parasites Trypanosoma cruzi and Leishmania (Leishmania) amazonensis. The phenantrenoid 9,10-dihydro-4-methoxyphenanthren-2,7-diol 2 was active against Hela and Siha cells (CC50 5.86 ± 0.19 and 20.78 ± 2.72 μg/mL, respectively). Sub-lethal concentrations of the flavone rhamnazin 4 were not able to rescue the viability of the Vero cells infected by Zika virus.