Sheila Rodrigues Oliveira

Development of Sulfadiazine-Decorated PLGA Nanoparticles Loaded with 5-Fluorouracil and Cell Viability

The aim of this work was to synthesize sulfadiazine-poly(lactide-co-glycolide) (SUL-PLGA) nanoparticles (NPs) for the efficient delivery of 5-fluorouracil to cancer cells. The SUL-PLGA conjugation was assessed using FTIR, 1H-NMR, 13C-NMR, elemental analysis and TG and DTA analysis. The SUL-PLGA NPs were characterized using transmission and scanning electron microscopy and dynamic light scattering. Additionally, the zeta potential, drug content, and in vitro 5-FU release were evaluated. We found that for the SUL-PLGA NPs, Dh = 114.0 nm, ZP = −32.1 mV and the encapsulation efficiency was 49%. The 5-FU was released for up to 7 days from the NPs. Cytotoxicity evaluations of 5-FU-loaded NPs (5-FU-SUL-PLGA and 5-FU-PLGA) on two cancer cell lines (Caco-2, A431) and two normal cell lines (fibroblast, osteoblast) were compared. Higher cytotoxicity of 5-FU-SUL-PLGA NPs were found to both cancer cell lines when compared to normal cell lines, demonstrating that the presence of SUL could significantly enhance the cytotoxicity of the 5-FU-SUL-PLGA NPs when compared with 5-FU-PLGA NPs. Thus, the development of 5-FU-SUL-PLGA NPs to cancer cells is a promising strategy for the 5-FU antitumor formulation in the future.

In vitro studies of the activity of dithiocarbamate organoruthenium complexes against clinically relevant fungal pathogens.

The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1–C9 was investigated and assessed for its activity against four different fungal species with clinical interest and related to invasive fungal infections (IFIs), such as Candida spp. [C. albicans (two clinical isolates), C. glabrata, C. krusei, C. parapsolisis, C. tropicalis, C.dubliniensis (six clinical isolates)], Paracoccidioides brasiliensis (seven clinical isolates), Cryptococcus neoformans and Sporothrix schenckii. All synthesized complexes C1–C9 and also the free ligands L1–L9 were submitted to in vitro tests against those fungi and the results are very promising, since some of the obtained MIC (minimal inhibitory concentration) values were very low (from 10−6 mol mL−1 to 10−8 mol mL−1) against all investigated clinically relevant fungal pathogens, except for C. glabrata, that the MIC values are close to the ones obtained for fluconazole, the standard antifungal agent tested. Preliminary structure-activity relations (SAR) might be suggested and a strong influence from steric and lipophilic parameters in the antifungal activity can be noticed. Cytotoxicity assays (IC50) showed that the complexes are not as toxic (IC50 values are much higher—30 to 200 fold—than MIC values). These ruthenium complexes are very promising lead compounds for novel antifungal drug development, especially in IFIs, one of most harmful emerging infection diseases (EIDs).

Influence of oxidation state of sulfur on the dissociation of [Tz‐(CH2)n‐S(O)m‐(CH2)n‐Tz + Na+] adducts generated by electrospray ionization (Tz = tetrazole ring; n = 2, 3; m = 0, 1, 2)

Sodium adducts of six organosulfur-α,ω-ditetrazole compounds (Tz-(CH(2))(n)-S(O)(m)-(CH(2))(n)-Tz; where Tz = tetrazole ring; n = 2, 3; m = 0, 1, 2) were generated via electrospray ionization (ESI) and their fragmentation pattern assessed via collision-induced dissociation (CID). Two main dissociation channels were observed: (a) losses of N(2) and HN(3) from the tetrazole rings; (b) cleavage of the C-S bond. The sulfoxides pass predominantly through the second fragmentation pathway, but for the sulfides and sulfones the tetrazole ring fragmentation occurs. Theoretical calculations at the B3LYP/6-31 + G(d,p) level indicate that for all the adducts (sulfide, sulfoxide, and sulfone) the dissociation pathway that leads to product ions arising from loss of N(2) was the most exothermic. Based on these results and assumptions, it was postulated that the dissociation of the sulfoxide adducts occurs under kinetic control (N(2)-loss pathway via a much more energetic transition state). For the sulfide and sulfone adducts, on the other hand, the dissociation process takes place via a thermodynamically controlled process.

As práticas educativas e seus personagens na visão de estudantes recém-ingressados nos cursos de Química e Biologia

Resumo: Desenvolvemos o presente trabalho com o objetivo de identificar concepcoes sobre as relacoes em sala de aula apresentadas por alunos recem-ingressados nos cursos de Quimica e Biologia. Baseados em Bruner, usamos a narrativa como instrumento investigativo dessas concepcoes, solicitando aos alunos que se imaginassem professores e relatassem como seria um dia de suas vidas. Pela analise dos relatos, percebemos que o professor e aquele que estuda e se prepara para as aulas, transmite conhecimentos, motiva, contextualiza, tem uma boa relacao com os alunos e e admirado por eles. Alem disso, esse professor e considerado um profissional em tempo integral, trabalhando, sobretudo, no Ensino Medio, com alunos interessados e atenciosos. Entender como essas concepcoes se formaram e problematiza-las na formacao inicial e importante. Palavras-chave: Ensino de Quimica. Ensino de Biologia. Relacoes em sala de aula. Narrativas. Concepcoes.

Síntese e caracterização de novos copolímeros fosforilados

The rapid development in polymer chemistry has, in recent years, led to the introduction of polymeric materials in the field of medicine. Two major groups of polymers are used for medical applications: prosthetic and biologically active materials. We synthesized copolymers with the main chain consisting of poly (methyl methacrylate) and graft chains of poly(ethylene glycol) (COP GRAFT). Changes were made in the graft copolymer chains for a possible incorporation of a drug, such that it may be used for the controlled release of drugs. The synthesis of these new compounds is based on two synthetic routes and FTIR, differential scanning calorimetry (DSC), thermogravimetry (TGA) and X-ray diffraction (XRD) characterized the products formed at the end of each stage. Through FTIR we observed absorption bands characteristic of P-H, P=O and P-O bonds that were inserted into the polymer chain during phosphorylation of the COP GRAFT, beyond the absorption bands characteristic of the copolymer before phosphorylation, such as C=O and C-O. By TGA and DSC we observed that only the diisobutyl copolymer has endothermic transition temperature and degradation behavior consistent with a polymer. XRD results showed a structural and conformational change in crystallinity of modified chains. Molecular weight and polydispersity of COPGRAFT obtained by GPC increased after phosphorylation with diisobutyl group. The phosphorylation reaction was efficient in obtaining diisobutyl copolymer and the applied techniques confirmed the modification of the COPGRAFT chains.

In vitro susceptibility of Aspergillus spp. to dithiocarbamate organoruthenium compounds

The in vitro antifungal activity of ruthenium dithiocarbamate compounds (1–5) was investigated and assessed for its activity against seven different species of Aspergillus (Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus nomius, Aspergillus tamarii and Aspergillus terreus). Analysis of in vitro susceptibility was performed using broth microdilution assay following the Clinical and Laboratory Standards Institute guidelines for filamentous fungi. The cytotoxicity was evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Aspergillus clavatus and A. fumigatus were more susceptible species for complexes 1 and 2. Other complexes showed excellent minimum inhibitory concentration (4–64 μg ml−1) against most microorganisms. Complexes 1 and 2 are respectively 180‐ and 95‐fold more active than the corresponding free ligands against A. clavatus and the complex 5 is 46‐fold more active than free ligand against A. niger. Aspergillus niger was more susceptible to the action of the complexes 1 and 5 (16 μg ml−1). A low cytotoxic activity (IC50 > 10−6 mol l−1) on normal mammalian cells (BHK‐21) to the evaluated complexes was measured. Ruthenium complexes are promising antifungal agents against the development of novel effective drug against different species of Aspergillus; however, for A. nomius and A. terreus, they were not active in the highest concentration tested.

Ensinar e aprender Química: a percepção dos professores do Ensino Médio

O presente trabalho buscou investigar a percepcao dos professores da educacao basica sobre as praticas pedagogicas em sala de aula e na escola, as dificuldades enfrentadas e as possiveis maneiras de soluciona-las, assim como as formas por eles utilizadas para se manterem atualizados. A investigacao envolveu 93 professores do Ensino Medio de escolas do estado de Minas Gerais, durante a realizacao da Olimpiada Mineira de Quimica (OMQ) 2008. A analise dos comentarios feitos pelos professores, no instrumento de coleta de dados utilizado, mostrou que os mesmos tendem a associar as dificuldades que enfrentam principalmente a escola, aos alunos e a questoes externas a escola, ou seja, nao se assumem como parte dos problemas. Percebemos, tambem, que associam as principais melhorias na educacao basica a infra-estrutura da escola e que nem todos participaram de eventos que promovessem a atualizacao profissional nos ultimos dois anos.

ALGUMAS QUESTÕES AMBIENTAIS PERMEANDO O ENSINO DE QUÍMICA: O QUE PENSAM OS ESTUDANTES

The major goal of our research is the investigation of the perception of high school students in four schools in Belo Horizonte about environmental impacts. It was observed that even after high school conclusion, it is hard to explain the environmental impacts showed by usual national media. After data analysis, it was noticed that non-scientific point of view predominates in the students.

Antifungal activity of tri- and tetra-thioureido amino derivatives against different Candida species.

The in vitro antifungal activity of six thioureido substituted amines (P1–P6) was evaluated against Candida species, including Candida albicans, C. glabrata, C. krusei and C. parapsilosis. These tri‐ and tetra‐thioureido amino derivatives with different methylation levels were synthesised through easy synthetic routes to evaluate their antifungal properties against Candida species. Among all studied derivatives, the tri‐(2‐thioureido‐ethyl)‐amine (P1) was the most active compound inhibiting C. albicans and C. glabrata at a concentration of 0.49 μg ml−1; P3, the N,N′,N′′,N′′′‐hexamethyl‐derivative, also showed inhibitory activity against C. albicans and C. glabrata, but in higher concentrations (250 μg ml−1). The N,N′,N′′,N′′′‐tetramethylated amine (P5) only inhibited the growth of C. glabrata, but its corresponding N,N′,N′′,N′′′‐octamethyl derivative (P6) was also active against C. glabrata (125 μg ml−1) and it was the only compound active against C. parapsilosis. P2 and P4 showed no significant antifungal activity. The structure–activity relationship of the thioureido‐substituted derivatives indicates that the molecular branching and the alkylation levels can influence the antifungal activity. This study demonstrated that thioureido derivatives exhibited significant antifungal activity against Candida species and that they can be considered as a very promising bioactive lead compound to develop novel antifungal agents.

Estudos de relações estrutura-atividade quantitativas (QSAR) de bis-benzamidinas com atividade antifúngica

This paper describes 2D-QSAR and 3D-QSAR studies against Candida albicans and Cryptococcus neofarmans for a set of 20 bisbenzamidines. In the studies of 2D-QSAR with C. albicans it was obtained a correlation between log MIC-1 and lipolo component-Z (r2 = 0.68; Q2 = 0.51). In the case of C. neofarmans a correlation between log MIC-1 and lipolo component-Z and of Balaban index (r2 = 0.85; Q2 = 0.6) was obtained. 3D-QSAR studies using CoMFA showed that the steric fields contributed more to the predicted activities for Candida albicans (94.9%) and Cryptococcus neofarmans (97.9%).