Stemodin (1) is a diterpene produced by Stemodia maritima L. (Scrophulariaceae) and shows antiviral and tumor cell proliferation inhibitory activities. Chemical modifications of 1 were performed to produce the known stemodinone (2), two new stemodinone oximes, Z (3) and E (4), and seven new oxime esters derivatives (5, 6, 7, 8, 9, 10, and 11). All derivatives were evaluated for their cytotoxic activity in HL60 (promyelocytic leukemia), SNB-19 (astrocytoma), HCT-116 (colon carcinoma), and PC3 (prostate) human cancer cell lines, and L929 (healthy murine cells). Oximes 3 and 4 showed lower cytotoxic values than 1 against all cancer cell lines tested. However, esters 9 and 10 exhibited cell growth inhibition percentages higher than 1 against PC3, SNB-19, and HCT-116 cancer cell lines, ranging from 62.96 to 94.27%. Many of these values exceed that presented by doxorubicin (66.05-86.87%). All compounds showed no cytotoxic effect on healthy cells at the tested concentration of 25 µg mL-1. (1 L Scrophulariaceae (Scrophulariaceae activities 2, 2 , (2) oximes (3 4, (4) 5, 5 (5 6 7 8 11. 11 . 11) HL HL6 promyelocytic leukemia, leukemia leukemia) SNB19 SNB 19 SNB-1 astrocytoma, astrocytoma (astrocytoma) HCT116 HCT 116 HCT-11 colon carcinoma, carcinoma carcinoma) PC prostate (prostate L92 cells. cells) However SNB19, 19, 6296 62 96 62.9 9427 94 27 94.27% 66.0586.87%. 66058687 66.05 86.87% 66 05 86 87 (66.05-86.87%) mL1. mL1 mL 1. mL-1 ( (2 (4 SNB1 SNB- (astrocytoma HCT11 HCT-1 L9 629 62. 942 94.27 0586 66.0586.87% 6605868 6605 66.0 8687 86.87 0 (66.05-86.87% mL- HCT1 HCT- 94.2 058 66.0586.87 660586 660 66. 868 86.8 (66.05-86.87 94. 66.0586.8 66058 86. (66.05-86.8 66.0586. (66.05-86. 66.0586 (66.05-86 66.058 (66.05-8 (66.05- (66.05 (66.0 (66. (66 (6

Toads of the Rhinella genus have a pair of paratoid glands that store biological secretions of high toxicity and varied chemical composition, rich in biologically active compounds. The present work aimed to carry out the investigation of the metabolomic profile and evaluation of the biological potential of the secretion paratoid glands (PGS) from Rhinella granulosa. The paratoid secretion was collected in the Piauí state (Brazil), extracted with methanol and the extract was analyzed by ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Fifty chemical constituents were identified. The extract showed cytotoxicity against tumor cell lines of the central nervous system (half maximal inhibitory concentration (IC50) = 1.9 µg mL-1) and prostate (IC50 = 1.6 µg mL-1), unsatisfactory antimicrobial potential (minimal inhibitory concentration (MIC) > 312 µg mL-1) and inhibited the enzyme acetylcholinesterase (IC50 = 5.119 mg mL-1). The results presented relevant information about the PGS and contributed to the understanding of the metabolomic and biological potential of R. granulosa. composition compounds (PGS granulosa Brazil, Brazil , (Brazil) ultraperformance ultra performance timeofflight time flight spectrometry identified half IC50 IC 19 1 9 1. mL1 mL mL-1 (IC5 16 6 mL1, minimal MIC (MIC 31 5119 5 119 5.11 mL1. . R (Brazil IC5 mL- (IC 3 511 11 5.1 51 5.

The main objective of this work was to develop a nanoemulsion based on linseed oil and betulinic acid, stabilized with Pluronic F127 and polyglycerol polyricinoleate, for anticancer applications. The nanoemulsions were synthesized by ultrasound and evaluated for in vitro cytotoxicity, particle size, polydispersity index, zeta potential, morphology, encapsulation efficiency, storage stability, rheology and in vitro release kinetics. In vitro cytotoxicity assays were performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (72 h) against HCT-116 (colorectal carcinoma), SNB-19 (glioblastoma), NCI-H460 (lung carcinoma) and L-929 (normal fibroblasts) cells. The determination of 50% inhibitory concentration (IC50) showed an increased selectivity for the emulsified betulinic acid when compared to its free form for the HCT-116 cells. The IC50 values for the synthesized nanoemulsions showed a range from 3.2 to 3.7 µM (HCT-116), 5.6 and 11.5 µM (NCI-H460), 5.8 and 7.3 µM (SNB-19) and > 16.5 µM for normal fibroblasts. In the 48 h in vitro release assays, it presented controlled release explained by the Korsmeyer-Peppas model, releasing 572.25 and 619.95 µg of betulinic acid in a controlled way, generating promising perspectives for the prolonged release of betulinic acid in anticancer applications.

The genus Chamaecrista comprises more than 330 species, with only a few studies on their chemical composition and biologic activities. In this study, the phytochemical profile of leaf, stems, and fruits extracts of the C. duckeana were examined by UPLC ESI HRMS analysis to determine possibly bioactive constituents. The antioxidant activity was carried out through in vitro assay, by the sequestration of the free radical DPPH. To evaluate the cytotoxic activity of the extracts, an MTT assay was used and the IC50 was determined against HL60 and RAJI cell lines. The metabolic profiles of the botanical parts are dominated by flavonoid class, highlighting isoflavonoids such as daidzin and ononin. All these compounds are reported for the first time in C. duckeana. The extracts presented antioxidant potential, and the activity of the stems extract was higher than the standard butylated hydroxytoluene. In the cytotoxic assay, only HL60 line (leukemia) had growth inhibition over 80%. The stems presented more expressive cytotoxicity with IC50 of 137.3 (104.6-180.1) and 106.8 (96.52-118.3) μmol. L-1 for HL60 and RAJI, respectively. In conclusion, the present work provides an in-depth knowledge about the chemical profile of C. duckeana, a species rich in bioactive secondary metabolites with cytotoxic activity.

Cinnamic acid and its derivatives show a remarkable variety of biological activities and are often studied in search of the development of new and highly effective drugs. This work aims to synthesize, characterize and evaluate the cytotoxic activity of esters derived from cinnamic acid. Eighteen esters were synthesized through Steglich’s esterification, of which eleven were not reported in the literature. All compounds were fully characterized by Fourier transform infrared epectroscopy (FTIR), nuclear magnetic resonance (1H and 13C NMR) and high-resolution mass spectrometry (HRMS) data. The cytotoxic activity of esters obtained was evaluated using four human tumor cell lines: SNB-19 (astrocytoma), HCT-116 (colon carcinoma, human), PC3 (prostate) and HL60 (promyelocytic leukemia) through the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) colorimetric assay. These studies showed that the compound 3-methoxybenzyl (E)-3-(4-methoxyphenyl)acrylate (12) is the most potent against HCT-116, PC3 and SBN-19 cells, with the lowest half maximal inhibitory concentration (IC50) value of 16.2 µM in the HCT-116 strain. The derivatives were obtained in good yields (76.6-95%), except for compounds 5-isopropyl-2-methylphenyl (E)-3-(3-hydroxy-4-methoxyphenyl)acrylate (17) (18.6%) and 2-isopropyl-5-methylphenyl (E)-3-(3-hydroxy-4-methoxyphenyl)acrylate (18) (15.5%).

Rhinella jimi toads (Stevaux, 2002) belong to the Bufonidae family, are endemic in the Brazilian Northeast and are commonly found during rainy periods. In general, amphibians of this family have in their poisons different metabolites that show a diversity of pharmacological activities. The isolation and identification of these compounds are of great importance, and techniques such as high-performance liquid chromatography coupled to mass spectrometry are widely used for the discovery of novel and known compounds in these poisons. For R. jimi poison, the ethyl acetate and methanolic extracts were obtained and thirty compounds were identified by combining ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) with direct infusion atmospheric pressure chemical ionization mass spectrometry (DI-APCI-MS/MS) and direct infusion electrospray mass spectrometry (DI-ESI-MS/MS) for each extract, respectively. Marinobufagin (2) and marinobufotoxin (19) were the majorities of each extract, respectively. In addition, other bufadienolides mainly present in the ethyl acetate extract, such other bufotoxins, alkaloids and arginine diacid derivatives were identified in the methanol extract. In a cytotoxic assay by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), the extracts and compound 2 demonstrated half-maximal inhibitory concentration (IC50) values better than the positive control doxorubicin, evidencing excellent cytotoxic. This is the most complete study of the chemical composition of R. jimi toad poison and its respective cytotoxic activity, promoting the enrichment of knowledge about this family and species.

ABSTRACT Objective: To evaluate genotoxicity of zinc oxide, P. A. calcium hydroxide, mineral trioxide aggregate and an iodoform paste using comet assay on human lymphocytes. Material and Methods: Two positive controls were used: methyl-methanesulfonate for the P.A. calcium hydroxide and mineral trioxide aggregate; and doxorubicin for the iodoform paste and zinc oxide. There were also two negative controls: distilled water for the P.A. calcium hydroxide and mineral trioxide aggregate; and DMSO for the iodoform paste and zinc oxide. Comets were identified using fluorescence microscopy and 100 of them were counted on each of the three slides analyzed per drug test. A damage index was established, taking into consideration the score pattern that had previously been determined from the size and intensity of the comet tail. Analysis of variance, followed by Tukey’s test, was used to compare the means of the DNA damage indices. Results: The DNA damage index observed for mineral trioxide aggregate (7.08 to 8.58) and P.A. calcium hydroxide (6.50 to 8.33), which were similar to negative control index. On the other hand, damage index for zinc oxide (104.7 to 218.50) and iodoform paste (115.7 to 210.7) were similar to positive control index. Conclusion: Iodoform paste and zinc oxide showed genotoxicity at all concentrations used.

RESUMO INTRODUÇÃO: O local de trabalho é uma importante área de ação para a promoção de estilos de vida saudáveis. OBJETIVOS: Avaliar fontes de informação e temáticas que suscitam maior interesse sobre alimentação/nutrição, estado de saúde e conhecimentos sobre alimentação dos colaboradores de uma câmara municipal. METODOLOGIA: Participaram no estudo 118 colaboradores de uma câmara municipal. Foram recolhidos dados sociodemográficos, autoperceção do estado de saúde, peso e altura, fontes de informação e temas preferenciais sobre alimentação/nutrição e conhecimentos nesta área (recomendações dietéticas; fonte alimentar de nutrientes; relação dieta-doença) através do Questionário de Conhecimentos Nutricionais (QCN). RESULTADOS: As mulheres apresentaram nível superior de conhecimentos, quer no total (p = 0,001), quer nas secções relativa à fonte alimentar de nutrientes (p = 0,001) e à relação dieta-doença (p = 0,030). Também os participantes mais novos (R = -0,205; p = 0,030), com menor índice de massa corporal (R = -0,188; p = 0,049), maiores habilitações literárias (R = 0,506; p < 0,001) e que se autopercecionam mais saudáveis (R = 0,123) apresentaram nível superior de conhecimentos. A secção relativa à relação dieta- doença foi aquela em que se verificou menor nível de conhecimentos. Relativamente às fontes de informação, 67,8% relataram ter por hábito fazê-lo, principalmente na Internet (58,5%) ou através de um médico (30,5%). Os participantes que realizam pesquisa apresentaram um maior nível de conhecimentos (mediana = 67,2% vs. 57,8%; p = 0,004). Estudaram-se também as diferenças nos conhecimentos entre quem utilizava ou não cada fonte de informação. CONCLUSÕES: Estes resultados evidenciam que o nível de conhecimentos sobre alimentação neste grupo não é elevado, justificando a necessidade de implementar intervenções a nível da promoção da literacia alimentar/nutricional. Pelas suas características, a vertente da educação alimentar deve ser prioritária, bem como intervenções ao nível do ambiente alimentar no local de trabalho.

ABSTRACT INTRODUCTION: The workplace is an important area of action for the promotion of healthy lifestyles. OBJECTIVES: To evaluate sources of information and food/nutrition topics which arouse greatest interest, health status and nutritional knowledge among employees of a city hall. METHODOLOGY: One hundred eighteen employees of a city hall participated in the study. Sociodemographic data, self-perception of health status, weight and height, sources of information and preferential food/nutrition issues, and knowledge on this subject (dietary recommendations; food source of nutrients; diet-disease relationship) were obtained through the Nutritional Knowledge Questionnaire (NKQ). RESULTS: Females had higher level of knowledge, either in total (p = 0.001) and in the sections on food source of nutrients (p = 0.001) and on diet-disease relationship (p = 0.030). Also, younger participants (R = -0.205; p = 0.030), those with lower body mass index (R = -0.188; p = 0.049), those with higher academic qualifications (R = 0.506; p < 0.001) and those who perceived themselves as healthy (R = 0.123) had higher level of knowledge. The section on diet-disease relationship registered the lowest level of knowledge. Regarding sources of information, 67.8% reported the habit of doing it, mainly using the Internet (58.5%) and through a doctor (30.5%). Employees who research information had higher level of knowledge (median = 67.2% vs. 57.8%; p = 0.004). We also studied the differences on knowledge between participants who use or not each information source. CONCLUSIONS: These results show that, in this group, the level of knowledge about food/nutrition is not high, justifying the need to implement interventions in terms of promoting food/nutritional literacy. Given its characteristics, food education should be a priority, as well as interventions focusing food environment on the workplace.

Agroindustrial residues, such as leaves of fruit plants, can be sources of bioactive molecules, thus adding value to co-products that are rarely explored in agroindustry. In this context, this study aimed to look into the phytochemical profiles in detail and to explore the antitumor potential of S. tuberosa and S. mombin leaves. We observed that, S. tuberosa leaf extract was cytotoxic in both tumor and healthy cells. S. mombin extracts selectively inhibited cell proliferation in the tumor cell line for prostate cancer (PC3) and did not significantly affect healthy cells. The metabolic profiles of the extracts were evaluated by gas chromatography coupled with mass spectrometry and twenty-three metabolites were identified. The correlation of metabolic profiles with cytotoxic tests indicated possible chemical markers that may be responsible for the inhibition of cell proliferation. This study revealed that the unexplored co-products in agroindustry may have great therapeutic potential, and therefore should be screened for biologically active compounds.

A series of 2-hydroxy-3-arylnaphthalene-1,4-diones (3-aryllawsones) were synthesized by Suzuki-Miyaura cross coupling reaction of 3-iodolawsone with arylboronic acids/esters. The hydroxylated resulting products were transformed into their corresponding N,N-diethyl carbamates. The antineoplastic and antileishmanial activities of the compounds were evaluated and compared with lapachol and its carbamate, providing promising results.

ABSTRACT Human epidermal receptors (HER1/2/3/4) belong to the class of receptor-type tyrosine kinases. After binding a ligand, dimerization, it will ocurr activation of intracellular kinases after two-dimensional and cytoplasmic tail reciprocal transphosphorylation. This transphosphorylation recruits signaling pathways such as Ras/Raf/MEK/Erk1-2, PI3-K/AKT and JAK/STAT, which can affect the cell cycle, cytoskeleton reorganization, apoptosis, metastasis, differentiation, angiogenesis and transcription. HER deregulation is found in epithelial, mesenchymal and nervous neoplasms and is associated with poor prognosis and tumor severity. Since HER are promiscuous proteins when subjected to mutations, resultant modifications confer cellular metabolic superiority and activate complex, interconnected and overlapping networks of cytoplasmic signaling. Moreover, overexpression of HER1/2 is involved in tumor resistance to radiation and anti-hormone therapies. Indeed, HER2 expression is up to 100-fold higher in 25-30% of invasive breast cancers. These characteristics support the development of resistance to anti-HER1/2 chemotherapy such as monoclonal antibodies and tyrosine kinase inhibitors. Then, the challenges in research with HER-positive cancers include planning therapeutic strategies against known resistance mechanisms and identifying novel mechanisms as a way to overcome and control cell growth and malignant progression.

RESUMO Aniba riparia (Lauraceae) é uma importante planta medicinal encontrada na região amazônica que apresenta alcaloides do tipo alcamida e conhecidos como riparinas. Este trabalho teve como objetivo avaliar os efeitos antioxidantes, antitumorais e leishmanicidas in vitro da riparina A. Riparina A apresentou fraca capacidade antioxidante pelas técnicas do DPPH• (CE50 de 296,2 μg mL-1) e ABTS•+ (CE50 de 450,1 μg mL-1), mostrou moderada atividade contra carcinoma de cólon (HCT-116: CI50 de 21,7 μg mL-1) e atividade leishmanicida sobre formas promastigotas de Leishmania amazonensis (CI50 de 307,0 ± 79,6; 193,7 ± 44,3 e 81,8 ± 11,2 μg mL-1, respectivamente, após 24, 48 e 72 h de incubação). Assim, além de sua simplicidade estrutural, a riparina A revelou atividades biológicas promissoras e significativa ação leishmanicida in vitro, resultado importante diante da relevância epidemiológica para controle da leishmaniose no Brasil, inclusive na região amazônica.

ABSTRACT Aniba riparia (Lauraceae) is an important medicinal plant found in the Amazon region and presents alkaloids of the type alkamide known as riparins. Riparin A is structurally represented as the fundamental core of all Amazon riparins. This work aimed to assess the in vitro antioxidant, antitumor and antileishmanial effects of riparin A. Riparin A presented weak antioxidant capacity by tecniques of DPPH• (EC50 of 296.2 μg mL-1) and ABTS•+ (EC50 of 450.1 μg mL-1), showed moderate activity against colon carcinoma (HCT-116: IC50 of 21.7 μg mL-1) and leishmanicidal activity on promastigotes of L. amazonensis (IC50 of 307.0 ± 79.6, 193.7 ± 44.3 and 81.8 ± 11.2 μg mL-1, respectively, after 24, 48 and 72 h of incubation). Then, in addition to its structural simplicity, riparin A revealed promising biological activities and remarkable in vitro leishmanicidal action, an important result in epidemiological point of view to control leishmaniasis in Brazil, including in the Amazon region.

Specimens of Leonotis nepetiflolia were obtained from cultivated and wild environments to verify their influences in chemical composition. Phytochemical analyses were conducted for the ethyl acetate phase obtained by partitioning the crude ethanol extract from the cultivated leaves of L. nepetifolia. In doing so, flavonoid 3',4',5-trimethoxy-6,7-dihidroxyflavone (cirsiliol), a chemotaxonomic marker of the family Lamiaceae, was isolated. The results reveal that all phases and extracts tested exhibited weak to moderate antimicrobial activity against the strains of bacteria tested. The evaluation of in vitrocytotoxic and antitumor activity showed that the ethyl acetate phases obtained from both wild and cultivated leaves exhibit high potential cytotoxic and antitumor (> 78.0% of inhibition) activity. The major component of these phases was identified by high-performance liquid chromatography-diode array detector and nuclear magnetic resonance analyses using both 1D and 2D methods. The results further indicate that the flavonoid cirsiliol is the agent responsible for the activity observed in these phases.

RESUMOCasearia sylvestris Swartz é uma planta medicinal amplamente distribuída no Brasil. Ela possui atividade anti-inflamatória, antiulcerogênica e antitumoral e é popularmente utilizada para tratar envenenamentos ofídicos, ferimentos, diarreia, gripes e resfriados. Suas folhas são ricas em diterpenos clerodânicos tricíclicos oxigenados, particularmente casearinas. Aqui, nós avaliamos as atividades antioxidantes de um fração com casearinas (FC) isolada de C. sylvestrise as alterações histológicas no sistema nervoso central e fígados de camundongos Mus musculus. Primeiramente, estudos in vitro(0,9, 1,8, 3,6, 5,4 e 7,2 μg/mL) revelaram valores de CE50 de 3,7, 6,4 e 0,16 µg/mL para nitrito, radical hidroxila e níveis de TBARS, respectivamente. Em seguida, a FC (2,5, 5, 10 e 25 mg/kg/dia) foi administrada intraperitonealmente por 7 dias consecutivos em camundongos Swiss. Os níveis de nitrito no hipocampo (26,2, 27,3, 30,2 e 26,6 µM) e no corpo estriado (26,3, 25,4, 34,3 e 27,5 µM) aumentaram em todos os animais tratados com a FC (P < 0.05). As menores doses reduziram os níveis de glutationa reduzida, de catalase e de TBARS no hipocampo e no corpo estriado. Com exceção da redução na formação de TBARS, a FC demonstrou atividade antioxidante apenas in vitro. Os animais exibiram alterações histológicas que sugerem neurotoxicidade e hepatotoxicidade, indicando a necessidade de cuidados em relação ao consumo de preparações medicinais à base de Casearia sylvestris.

ABSTRACTCasearia sylvestris Swartz is a medicinal plant widely distributed in Brazil. It has anti-inflammatory, antiulcer and antitumor activities and is popularly used to treat snakebites, wounds, diarrhea, flu and chest colds. Its leaves are rich in oxygenated tricyclic cis-clerodane diterpenes, particulary casearins. Herein, we evaluated the antioxidant activities of a fraction with casearins (FC) isolated from C. sylvestrisand histological changes on the central nervous system and livers of Mus musculus mice. Firstly, in vitro studies (0.9, 1.8, 3.6, 5.4 and 7.2 μg/mL) revealed EC50 values of 3.7, 6.4 and 0.16 µg/mL for nitrite, hydroxyl radical and TBARS levels, respectively. Secondly, FC (2.5, 5, 10 and 25 mg/kg/day) was intraperitoneally administered to Swiss mice for 7 consecutive days. Nitrite levels in the hippocampus (26.2, 27.3, 30.2 and 26.6 µM) and striatum (26.3, 25.4, 34.3 and 27.5 µM) increased in all treated animals (P < 0.05). Lower doses dropped reduced glutathione, catalase and TBARS levels in the hippocampus and striatum. With the exception of this reduction in TBARS formation, FC displayed only in vitro antioxidant activity. Animals exhibited histological alterations suggestive of neurotoxicity and hepatotoxicity, indicating the need for precaution regarding the consumption of medicinal formulations based on Casearia sylvestris.

Onze derivados da ftalimida foram avaliados quanto a sua atividade antiproliferativa em células tumorais e normais e possíveis efeitos tóxicos. Avaliou-se a citotoxicidade contra tumores murinos (células de Sarcoma 180 e B-16/F-10) e células mononucleares do sangue perférico (CMSP) usando os ensaios de MTT e Alamar Blue. Em seguida, a investigação de citotoxicidade foi executada por citometria de fluxo e potencial antitumoral e toxicológico por meio de métodos in vivo. As moléculas 3b, 3c, 4 e 5 revelaram citotoxicidade in vitro contra Sarcoma 180, B-16/F-10 e PBMC. Uma vez que o composto 4 foi o derivado mais efetivo, ele foi escolhido para detalhar o mecanismo de ação após 24, 48 e 72h de exposição (22.5 e 45 µM). Células de Sarcoma 180 tratadas com o composto 4 mostraram desintegração de membrana, fragmentação de DNA e despolarização mitocondrial de maneira tempo e concentracão dependente. Os compostos 3c, 4 e 5 (50 mg/kg/dia) não inibiu o crescimento tumoral in vivo. Os animals tratados com o composto 4 exibiram aumento do total de leucócitos, linfócitos e no peso relativo do baço, diminuição de neutrófilos e hiperplasia da polpa branca esplênica. Os animais tratados apresentaram alterações histológicas reversíveis. A molécula 4 tem ação antiproliferativa in vitro provavelmente por ativação de apoptose, efeitos tóxicos reversíveis e exibiu propriedades imunoestimulantes que podem ser exploradas para atacar células neoplásicas.

Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells) and peripheral blood mononuclear cells (PBMC) using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM). Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day) did not inhibit in vivotumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells.