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.

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.

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.