Abstract Many of the drugs used to fight cancer cells induce various damage causing hepatotoxic effects which are characterized by tissue changes. The aim of the study is to know the possible effects of salazinic acid on livers of mice exposed to Sacoma-180. The tumor was grown in the animals in ascitic form and inoculated subcutaneously in the axillary region of the mouse developing the solid tumor. Treatment with salazinic acid (25 and 50 mg/kg) and 5-Fluorouracil (20 mg/kg) started 24-hours after inoculation and was performed for 7 days. To verify these effects, the qualitative method of histological criteria investigated in liver tissue was used. It was observed that all treated groups showed an increase of pyknotic nuclei in relation to the negative control. There was an increase in steatosis in all groups compared to the negative control but there was a decrease in the groups treated with salazinic acid in the 5-Fluorouracil. There was no necrosis in the salazinic acid treated groups. However, this effect was seen in 20% of the positive control group. Therefore, it can be concluded that salazinic acid did not show hepatoprotective action on mice but demonstrated a decrease in steatosis and absence of tissue necrosis.

Abstract The aim of the present study was to perform in vitro and in vivo assessments of the antineoplastic action of 4-amino-pyrimidine encapsulated in liposomes. Liposomes were prepared and characterized for particle size and drug encapsulation and submitted to long-term stability tests. Cytotoxicity assays were performed in HeLa cells. Antineoplastic activity was investigated using the experimental sarcoma 180 tumor in Swiss albino mice. Encapsulation efficiency was 82.93 ± 0.04% and no significant changes were found with respect to particle size or pH after centrifugation and mechanical agitation tests. The in vitro results at concentration of 20 μg/mL indicated a considerable reduction in cell viability after treatment with encapsulated pyrimidine (75.91%). The in vivo assays using the compounds in encapsulated and free forms and 5-fluorouracil achieved tumor inhibition rates of 66.47 ± 26.8%, 50.46 ± 16.24% and 14.47 ± 9.22%, respectively. Mitotic counts demonstrated a greater reduction in the number of mitoses in animals treated with liposomal pyrimidine (32.15%) compared to those treated with the pyrimidine free (87.69%) and 5-fluorouracil (71.39%). This study demonstrated that the development of liposome formulations containing 4-amino-pyrimidine is a promising alternative for overcoming limitations related to the toxicity of current cancer treatment, ensuring greater therapeutic efficacy.

The present study investigated the activity of pyrimidine derivatives against Aedes aegypti. Two compounds, 3c and 3d showed excellent larvicide activity. Additionally, quantitative structure-activity relationship (QSAR) models were built using multiple-linear regression and partial least squares with descriptors generated from Dragon and VolSurf+ software, respectively. The best model is obtained with multiple linear regression (MLR), leading to a robust model. Moreover, the QSAR model is validated by means of some internal validation techniques in order to check its reliability, quality and robustness for predicting the larvicidal activity against A. aegypti. The models confirmed that the three-dimensional structure of molecules, steric properties, hydrophobic polar surface area, log partition (logP) and a simple pattern of substituent groups as methyl, methoxy, and succinimide in the pyrimidine derivatives are responsible for the larvicidal activity of the pyrimidine derivatives. Even more, the activity decreases by an electron-withdrawing group in R1 and increases when it is replaced by an aromatic ring activator group. These findings will aid in further studies of new pyrimidine derivatives active against Aedes aegypti.

ABSTRACT A series of arylamidines 3a-j was designed, synthesized and investigated for antimicrobial activity. Structures of the compounds were confirmed by IR, 1H-NMR and 13C-NMR and a 2D spectroscopic study was performed. A preliminary screening of the antimicrobial tests clearly showed that three out of ten arylamidines, viz, 3f, 3g and 3i, were effective against all the gram-negative bacteria: Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella enteric; and against the yeast, candida albicans. Further, the Minimum Inhibitory Concentrations (MIC) against the bacteria and yeast were determined. All compounds 3a-d, 3f, 3g, 3i and 3j were also investigated for their low cytotoxic effects on tested cell lines. Compounds 3d and 3f were the most effective derivatives against HL-60 and HEp-2 cells, respectively, with IC50 value (2µg/mL), and low normal cells toxicity.

ABSTRACT Phoradendron mucronatum and P. microphyllum are plants that found in tropical and subtropical areas, used in traditional medicine and popularly known as mistle-thrush. The aim of this study was to identify the chemical constituents of different leaf extracts from P. mucronatum and P. microphyllum and assess cytotoxic activity against strains from a human tumour cells. Extracts obtained with hexane, dichloromethane, chloroform and ethyl acetate from the leaves were analysed by gas chromatography coupled with mass spectrometry (GC-MS) and the cytotoxicity was assessed by the MTT method (bromide (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)). The tested human tumour cells were NCI-H292 (human pulmonar mucoepidermoid carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (epidermoid carcinoma of the larynx). Analysis by GC/MS of the extracts from leaves of P. microphyllum and P. mucronatum detected 51 different compounds, such as alkaloids, diterpenes, triterpenes, sterols, alcohols, aldehydes, fatty acids and hydrocarbons. In the cytotoxic evaluation, hexane and ethyl acetate extracts from the leaves P. microphyllum inhibited cell growth of NCI-H292 strains (72.97%) and HEp-2 (87.53%), respectively. The extracts of P. mucronatum species showed an inhibitory effect towards NCI-H292 (83.19%/hexane), MCF-7 (88.69%/dichloromethane) and HEp-2 (93.40%/hexane). The extracts showed cytotoxic activity against the tested strains, especially the P. mucronatum, which presented the highest percentages of inhibition of cell growth.

Studies of germination behavior and seedling establishment contribute to the development of appropriate methods of forest species management. The aim of this study was to investigate germination and seedling growth of tamboril (Enterolobium contorsiliquum (Vell.) Morong), taking into account environmental factors and seed weight. Seeds were separated into three weight classes (light, medium and heavy), to determine the moisture content percentage and thousand-seed weight per class. Seeds from each class were then tested for germination. The experimental design was completely randomized with a 2x3x4 factorial arrangement of treatments: two light conditions (presence and absence), three weight classes (Light < 0.7 g; Medium 0.7 to 0.8 g; Heavy > 0.8 g) and four temperatures (20, 30, 40 and 20-30 °C), with four replications each. Percentage of germination and germination speed index for seed vigor were determined. For the evaluation of seedling growth, the length and dry mass of both the shoot and root were determined. When the data proved normal, ANOVA and Tukey tests (p≤0.05) were conducted to compare treatment means. Non-normal data were analyzed using nonparametric Mann-Whitney test (p≤0.05). Germination speed index, shoot dry mass and root dry mass data presented a normal distribution, allowing for ANOVA testing. Germination occurred regardless of light conditions, with a higher speed at 40 °C, although this temperature was detrimental to seedling growth. The temperature of 30 °C promoted better germination (>80 %) and seedling growth. Heavy seeds displayed improved germination and produced more vigorous seedlings.

Los estudios del comportamiento de la germinación y el establecimiento de las plántulas contribuyen al desarrollo de métodos adecuados del manejo de especies forestales. El objetivo de este estudio fue investigar la germinación y crecimiento de plántulas de tamboril (Enterolobium contorsiliquum (Vell.) Morong), tomando en cuenta factores ambientales y el peso de las semillas. Las semillas se separaron en tres categorías de peso (ligeras, intermedias y pesadas) para determinar el porcentaje de contenido de humedad y peso de mil semillas por clase. La germinación de cada clase de semillas se evaluó. El diseño experimental fue completamente al azar con un arreglo factorial de tratamientos 2x3x4: dos condiciones de luz (presencia y ausencia), tres clases de peso (ligeras < 0.7 g, medianas 0.7 a 0.8 g y pesadas > 0.8 g) y cuatro temperaturas (20, 30, 40 y 20 a 30 °C), con cuatro repeticiones cada uno. El porcentaje de germinación e índice de velocidad de germinación fueron evaluados. Para crecimiento de las plántulas se midió la longitud y masa seca del vástago y de la raíz. Con los datos probados normales, se realizó ANDEVA y pruebas de Tukey (p≤0.05) para comparar las medias de los tratamientos. Los datos no normales se analizaron con la prueba no paramétrica Mann-Whitney (p≤0.05). El índice de velocidad de germinación, la masa seca del vástago y de la raíz presentó una distribución normal, lo que permitió realizar el ANDEVA. La germinación se produjo independientemente de la condición de luz, con velocidad mayor a 40 °C, aunque esta temperatura fue perjudicial para el crecimiento de las plántulas. La temperatura de 30 °C promovieron la germinación (>80%) y el crecimiento de las plántulas. Las semillas con peso mayor mostraron mayor germinación y produjeron plántulas más vigorosas.

Due to its folk use, scientific reports and phytochemical screening, the purpose of this work was to study the phytochemical and the biological properties of the methanol extract and to evaluate the anti-inflammatory activity as well as determine the acute toxicity, antitumor and cytotoxic activity of the root barks of Guettarda platypoda DC., Rubiaceae. In this analysis the presence of flavonoids and therpenoids were identified. These data and the ones in the literature indicated it as a potential antioxidant and motivated the cytotoxic analysis related with three tumoral cell strains as well as to evaluate its antitumoral activity (sarcoma 180 and Ehrlich carcinoma) in female mice. Due to the presence of esteroids and the previous study of the ethanolic extract, its anti-inflammatory activity and toxicity were also evaluated. Absence or low toxicity in 2000 mg/kg doses was verified and the attention to their phytochemical and pharmacological properties is constantly increasing.

Neste estudo descritivo exploratório avaliou-se as características biomecânicas do salto vertical de crianças de diferentes estágios maturacionais (inicial, elementar e maduro) segundo modelo de Gallahue (1989). Especificamente as variáveis entre os estágios foram caracterizadas e comparadas e foi verificada a contribuição de diferentes variáveis no desempenho. Participaram 39 escolares, seleccionados pelo processo casual sistemático. Utilizou-se uma plataforma de força extensométrica a 900 Hz, uma filmadora a 60 Hz e a matriz analítica de Gallahue (1989). Os dados dinâmicos foram normalizados pelo peso corporal, processados no sistema Peak Motus e filtrados via FFT Butherworth 4ª ordem passa baixa, corte a 30 Hz. Analisou-se: pico e gradiente de propulsão, impulso vertical, impacto, tempo de vôo e ângulos de quadril e joelho na propulsão, vôo e queda. Utilizou-se a estatística descritiva, a ANOVA one-way com post-hoc de Scheffé e a regressão linear múltipla, com p≤0,05. Verificou-se diferenças significativas entre os estágios no tempo de vôo e ângulo de quadril nas três fases do salto e ângulo de joelho no ápice do vôo. O impulso vertical foi a variável que teve maior contribuição na performance. As crianças do estágio maduro melhor coordenaram os segmentos corporais na execução do salto vertical.

This descriptive exploratory study evaluated biomechanical characteristics of vertical jump of children in different maturation stages (initial, elementary and mature) according to Gallahue’s model (1989). Specifically, variables of different stages were characterized and compared and the contribution of these variables to the performance was verified. The sample was composed by 39 scholars, selected through a systematic casual sampling process. An extensometric force plate sampled at 900 Hz, a 60 Hz video camera and Gallahue’s Analytical Matrix (1989) were used. Dynamic data were normalized by body weight, processed through Peak Motus System and filtered by a fourth-order low-pass Butterworth filter with a 30 Hz cut-off frequency. Analyzed variables: peak and gradient of propulsion, vertical impulse, impact, flight time, hip and knee angles during propulsion, flight and landing phases. Data were analyzed through descriptive statistics, ANOVA one-way followed by Scheffé post-hoc test and also Multiple Linear Regression (p≤0,05). One verified significant differences between the stages for flight time and hip angle during the three jump phases; and for knee angle during flight phase. Vertical impulse was the variable that most contributed to the performance. Children in mature stage presented better coordination of body segments during the vertical jump execution than children in other stages.

As atividades antiinflamatórias de oito compostos 4-amino-2,6-diarilpirimidina-5-carbonitrilas foram sujeitas a uma análise QSAR baseada nos resultados de cálculos de estrutura eletrônica B3LYP/6-31G(d,p) e AM1. Análise de Componentes Principais e regressões baseados nesses dados indicam que compostos potencialmente mais ativos teriam menores valores de momentos de dipolo e de coeficientes de partição e também seriam afetados pelos valores de cargas dos átomos de carbono através dos quais os dois anéis aromáticos estão ligados ao anel pirimidínico. Duas novas moléculas foram previstas serem, ao menos, tão ativas como aquelas com as maiores atividades usadas no estágio de construção do modelo. Uma delas, tendo o grupo metoxila conectado a um dos anéis aromáticos, foi prevista ter um valor de atividade antiinflamatória de 52,3%. Essa molécula foi sintetizada e sua atividade experimental foi determinada em 52,8%, em concordância com a previsão teórica AM1. Esse valor é 5% maior que o maior valor usado para a modelagem.

The experimental anti-inflammatory activities of eight 4-amino-2,6-diarylpyrimidine-5-carbonitriles were subjected to a QSAR analysis based on results from B3LYP/6-31G(d,p) and AM1 electronic structure calculations. Principal component analyses and regressions based on these data indicate that potentially more active compounds should have low dipole moment and partition coefficient values and also be affected by the values of the charges of the carbon atoms through which the two aromatic rings are bonded to the pyrimidinic ring. Two new molecules were predicted to be at least as active as those with the highest activities used in the model building stage. One of them, having a methoxy group attached to one of the aromatic rings, was predicted to have an anti-inflammatory activity value of 52.3%. This molecule was synthesized and its experimental activity was found to be 52.8%, in agreement with the AM1 theoretical prediction. This value is 5% higher than the largest value used for modeling.

Uma síntese fácil e eficiente de 3-aril-5[(1S)-t-butiloxicarbonil-1-amino-( 2S)-metil-1-butil)]-1,2,4-oxadiazóis 4a-f e 3-fenil-5-[(1S)-t-butiloxicarbonil-1-amino-1-etil]-1,2,4-oxadiazol 6 partindo de arilamidoximas, N-t-Boc-L-isoleucina e N-t-Boc-L-alanina é descrita. As estruturasedos intermediários e compostos finais foram determinadas a partir dos dados espectroscópicos.

A facile and efficient synthesis of 3-aryl-5-[(1S)-t-butyloxycarbonyl-1-amino-(2 S)-methyl-1-butyl)]-1,2,4-oxadiazoles 4a-f and 3-phenyl-5-[(1S)-t-butyloxycarbonyl-1-amino-1-ethyl]-1,2,4 -oxadiazole 6 starting from arylamidoximes, N-t-Boc-L-isoleucine and N-t- Boc-L-alanine is decribed. The structures of the intermediates and final compounds have been deduced from spectroscopic data.

A síntese de alguns derivados dos 1,2,4-oxadiazóis (4a-d) partindo das arilamidoximas apropriadas (1a-d) e do ácido N-t-butoxycarbonil-O-benzil-L-aspártico é descrita. As estruturas destes novos compostos foram determinadas por meios espectroscópicos.

The synthesis of some 1,2,4-oxadiazole derivatives (4a-d) starting from arylamidoximes 1a-d and N-t-butoxycarbonyl-O-benzyl-L-aspartic acid is described. The structures of these new products have been determined by spectroscopic methods.