This paper reports the DNA interaction and cytotoxicity of binary and ternary copper(II) complexes of valproic acid with phenanthroline or bipyridine and the complementary characterization of Cu(Valp)2Bipy by crystallography. Circular dichroism, plasmid and oligonucleotide assays have shown that the complexes interact with DNA in different manners and are able to cleave plasmid DNA and oligonucleotides at concentrations from 10 to 1000 mol L-1. The plasmid DNA cleavage is enhanced 650, 375 and 285 times by photo activation with UVB light for the complexes Cu(Valp)2Phen, Cu(Valp)2Bipy and Cu2(Valp)4, respectively. Cytotoxicity assays demonstrated that V79 cells were more sensitive to CuII derivatives than sodium valproate as evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) and clonogenic assays, where the cytotoxic profile of the compounds was: Cu(Valp)2Phen higher than Cu(Valp)2Bipy, higher than Cu2(Valp)4. Therefore, we report two copper complexes, which interact with DNA and promote its cleavage, leading to an enhanced cytotoxicity when compared to valproic acid.

ABSTRACT Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.

O presente estudo descreve a acentuada atividade citotóxica da nor-β-lapachona, seus derivados arilamino substituídos, naftoquinonas iodadas e metilada, além de nor-β-lapachonas 1,2,3-triazólicas, contra quatro linhagens de células de leucemia humana (HL-60, K562, Molt-4 e Jurkat). Nor-β-lapachonas arilamino substituídas foram identificadas com potente atividade, revelando-se como potenciais protótipos contra as linhagens tumorais descritas. Estudos utilizando o ensaio cometa evidenciaram danos ao ácido desoxirribonucleico (ADN) causado pelos derivados arilamino substituídos devido o aumento dos níveis intracelulares de espécies reativas de oxigênio (ERO's). Células de HL-60 foram selecionadas para a continuidade dos estudos de mecanismos moleculares subjacentes e apoptose induzida pelos derivados quinoidais foi observada por análise de citometria de fluxo. Cepas de Saccharomyces cerevisiae foram utilizadas para uma investigação preliminar sobre o mecanismo de ação em topoisomerases de ADN. Os estudos sugerem que, aparentemente, a citotoxidade dos compostos não envolve a inibição de topoisomerases, mas que o tratamento prejudica a atividade de reparação do ADN, provocando assim a morte celular. A capacidade em induzir apoptose e aberrações cromossômicas em fibroblastos de pulmão de hamster chinês (células V79) também foi investigada. Núcleos apoptóticos foram observados e nossos estudos indicam uma correlação entre dano ao ADN e apoptose.

The current study describes that nor-β-lapachone and its arylamino derivatives, iodinated and methylated naphthoquinones and nor-β-lapachone-based 1,2,3-triazoles exhibited pronounced cytotoxic effects against four human leukemia cell lines (HL-60, K562, Molt-4 and Jurkat). Nor-β-lapachones arylamino substituted with potent activity were identified, revealing themselves as potential prototypes against tumor cell lines. Moreover, cells treated with these compounds showed DNA damage according to the standard comet assay, a finding that was, at least in part, due to increased intracellular levels of ROS. HL-60 cells were chosen to study the underlying molecular mechanisms of cytotoxicity. Drug-induced apoptosis in HL-60 cells was observed by flow cytometry analyses. Strains of Saccharomyces cerevisiae were used for a preliminary investigation into the mechanism of drug action on DNA topoisomerases. These results suggested that the cytotoxicity of these compounds apparently does not involve topoisomerase inhibition, but that treatment impairs DNA repair activity, thus triggering cell death. Considering their pro-oxidant properties, we investigated the ability of these compounds to induce apoptosis and chromosomal aberrations as micronuclei in Chinese hamster lung fibroblasts (V79 cells). Morphological apoptotic nuclei and micronuclei induction following drug treatment were observed, suggesting a correlation between DNA damage and apoptosis.

O objetivo deste estudo foi avaliar os efeitos benéficos de extratos de folhas de videira (Vitis labrusca L.) orgânicas e convencionais em reduzir o dano gerado pelo peróxido de hidrogênio no fígado, coração e rim de ratos Wistar, pela medida de danos a lipídios e a proteínas (Ensaio Carbonyl), como também a modulação sob a atividade das enzimas antioxi-dantes superoxido dismutase e catalase. A pré-incubação com 5 mg/mL de extratos de folhas de videira (Vitis labrusca L.) orgânicas e convencionais previnem ambos danos oxidativos a lipídios e proteínas em todos os tecidos analisados. O extrato de folha orgânica foi capaz de restabelecer a atividade das enzimas superóxido dismutase (rim e fígado) e catalase (coração), as quais foram modificadas pelo tratamento com peróxido de hidrogênio. O extrato convencional foi capaz de restabelecer apenas a enzima catalase no fígado e no coração. Os efeitos do extrato da folha V. labrusca mostrados neste estudo, provavelmente, poderiam ser importantes para a formulação de suplementos dietéticos, bem como para o desenvolvimento de novos ingredientes com propriedades antioxidantes provenientes de outras plantas.

The purpose of this study was to evaluate the beneficial effects of organic and conventional grapevine (Vitis labrusca L.) leaf extracts in reducing hydrogen peroxide-induced stress in the liver, heart and kidney of Wistar rats by measuring lipids and proteins damages (carbonyl assay), as well as the activity of the antioxidant enzymes superoxide dismutase and catalase. The preincubation with 5 mg/mL of organic and conventional grapevine (Vitis labrusca L.) leaf extracts prevented both lipids and proteins oxidative damages in all tissues analyzed. The organic leaf extract was able to restore superoxide dismutase (kidney and liver) and catalase (heart) activities, which were modified by the treatment with H2O2. The conventional extract was able to restore only the catalase activity in liver and heart tissues. The beneficial effects of the V labrusca leaf extract shown in this study could probably be important for formulating dietary supplements, as well as for developing new ingredients with improved antioxidant properties from other plant sources.

O disseleneto de difenila (DPDS) é um reagente eletrofílico empregado na síntese de diversos compostos organoselenados (OS) farmacologicamente ativos. O objetivo do presente estudo foi investigar os efeitos mutagênicos de três derivados simétricos do DPDS (p-cloro-fenil-disseleneto, p-metil-fenil-disseleneto e p-metoxi-fenil-disseleneto) em levedura. Em resumo, os efeitos celulares dos três OS estudados nesse trabalho parecem ser variáveis em função do grupo químico substituinte no anel aromático e da concentração empregada. A presença de grupo metila no anel aromático do DPDS aumenta o potencial citotóxico enquanto a inserção de um grupamento metoxila potencializa os efeitos citotóxicos e mutagênicos do DPDS.

Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a variety of pharmacologically active organoselenium (OS) compounds. The aim of the present study was to investigate the mutagenic effects of three symmetrical derivatives from the prototype DPDS (p-chloride-phenyl-diselenide, p-methyl-phenyl-diselenide and p-methoxy-phenyl-diselenide) in yeast. In summary, the cellular effects of the three OS compounds studied in this work appear to be variable according to the substituent group in the aromatic ring and are concentration-dependent. The presence of methoxyl group in the aromatic ring of DPDS structure results in elevation of the cytotoxic and mutagenic potential while the introduction of a methyl group increases the cytotoxic effect.

Aqueous extracts of seven species used in Brazilian popular medicine (Achyrocline satureoides, Iodina rhombifolia, Desmodium incanum, Baccharis anomala, Tibouchina asperior, Luehea divaricata, Maytenus ilicifolia) were screened to the presence of mutagenic activity in the Ames test (Salmonella/microsome). Positive results were obtained for A. satureoides, B anomala and L. divaricata with microsomal activation. As shown elsewhere (Vargas et al., 1990) the metabolites of A. satureoides extract also show the capacity to induce prophage and/or SOS response in microscreen phage induction assay and SOS spot chromotest.