A large number of quinones have been associated with antitumor, antibacterial, antimalarial, and antifungal activities. Results of previous studies of 5-methoxy-3,4-dehydroxanthomegnin, a naphthoquinone isolated fromPaepalanthus latipes Silveira, Eriocaulaceae, revealed antitumor, antibacterial, immunomodulatory, and antioxidant activities. In this study, we assessed the mutagenicity and metabolism-mediated cytotoxicity of 5-methoxy-3,4-dehydroxanthomegnin by using the Ames test and a microculture neutral red assay incorporating an S9 fraction (hepatic microsomal fraction and cofactors), respectively. We also evaluated the mutagenic activity inSalmonella typhimurium strains TA100, TA98, TA102, and TA97a, as well as the cytotoxic effect on McCoy cells with and without metabolic activation in both tests. Results indicated that naphthoquinone does not cause mutations by substitution or by addition and deletion of bases in the deoxyribonucleic acid sequence with and without metabolic activation. As previously demonstrated, the in vitro cytotoxicity of 5-methoxy-3,4-dehydroxanthomegnin to McCoy cells showed a significant cytotoxic index (CI50) of 11.9 μg/ml. This index was not altered by addition of the S9 fraction, indicating that the S9 mixture failed to metabolically modify the compound. Our results, allied with more specific biological assays in the future, would contribute to the safe use of 5-methoxy-3,4-dehydroxanthomegnin, compound that has showed in previous studies beneficial properties as a potential anticancer drug.

Cancer constitutes the second main mortality cause in the world, after cardiovascular diseases. In spite of the progresses in the chemotherapeutics treatments, many patients fail chemotherapy, mainly because of side effects or multi-drugs resistance, proving the need and importance of the research for new molecules with anticancer activity, more effective and with smaller adverse effects. Various compounds derived from plant secondary metabolites are commonly used in the chemotherapy against cancer and the natural products play an important role in the research for new molecules. Among several molecules of natural origin evaluated by MTT assay in murine tumor cell lines [breast (LM3) and lung (LP07)] the quinona-methide triterpenes tingenone and pristimerin showed marked cytotoxic activity presenting IC50 around 2 and 5 µM respectively. The structure-activity relationship suggests that rings A and B containing an α, ß-unsaturated carbonyl group are essential for the observed cytotoxic activity. The interaction between these positions and acetylcisteyne residues suggests a probable mechanism of action. The in vitro mutagenic activity was also evaluated by the Salmonella microsome assay (Ames test) for pristimerin and tingenone with and without metabolic activation (S9) in the strains TA98, TA97a, TA100 and TA102, none of which showed mutagenic potential in any strains. Estrogenic and anti-estrogenic activities were also studied by the e-screen assay in MCF-7 cells with negative results. The present data point to the importance of pristimerin and tingenone as representative of an emerging class of potential anticancer chemicals.

Currently, a wide range of research involving natural products is focused on the discovery of new drugs in many different therapeutic areas. A great number of the synthetic compounds on the market were derived from natural products, especially plants. Nemorosone is the major constituent of the floral resin of Clusia rosea Jacq., Clusiaceae, and in Cuban propolis. In vitro studies have shown cytotoxic activity in this substance against various tumor cell lines, including those resistant to various cytotoxic drugs, whereas it has low cytotoxicity to non-tumoral cells. Therefore, in order to characterize the biological activity of nemorosone, a substance with potential antitumor activity, and in view of preclinical testing of the toxicity of drug candidate compounds, the main aim of this study was to determine the mutagenic and antimutagenic activity of nemorosone by the Ames test, using the strains TA97a, TA98, TA100 and TA102 of Salmonella typhimurium. Secondly, to characterize the estrogenic activity in an experimental recombinant yeast model (Recombinant Yeast Assay) mutagenic activity was observed at in any of the concentrations in any of the test strains. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine (NPD), mitomycin C (MMC) and aflatoxin B1 (AFL). Nemorosone showed moderate antimutagenic activity (inhibition level 31%), in strain TA100 in the presence of AFL, and strong antimutagenic activity in TA102 against MMC (inhibition level 53%). Estrogenic activity was observed, with an EEq of 0.41±0.16 nM at various tested concentrations.

Algumas espécies de plantas do gênero Alchornea (Euphorbiaceae) são conhecidas por apresentarem as atividades biológicas: antioxidante, antifúngica, antiinflamatória, antibacteriana, citotóxica para células tumorais e inibidoras da replicação dos vírus HIV-1 e HIV-2. São também amplamente usadas na medicina popular na America do Sul e África. No Brasil, Alchornea castaneaefolia Willd. A. Juss. e Alchornea glandulosa Poepp. & Endl. são usadas para tratamento do reumatismo, artrite e dores musculares. Devido ao uso medicinal dessas plantas e o potencial risco do seu consumo indiscriminado, no presente trabalho foi avaliada a atividade mutagênica dos extratos metanólico e clorofórmico das folhas, empregando o teste do micronúcleo in vivo e o teste de Ames. Os resultados mostraram que o extrato clorofórmico não apresentou mutagenicidade, porém, o extrato metanólico de A. castaneaefolia foi mutagênico para a linhagem TA98 de Salmonella typhimurium e o extrato metanólico de A. glandulosa para as linhagens TA98 e TA97a. O extrato metanólico de ambas as espécies também apresentaram mutagenicidade positiva nos ensaios in vivo na maior concentração usada. Os prováveis agentes mutagênicos envolvidos foram a quercetina aglicona e amentoflavona presentes em ambas as espécies.

Some species of the plant genus Alchornea (family Euphorbiaceae) are widely used in popular medicine, mainly in South America and in Africa. Several kinds of biological activity have been seen in the species: antioxidant, antifungal, anti-inflammatory, antibacterial, cytotoxic against tumor cell lines and inhibitory to the replication of HIV-1 and HIV-2. In Brazil, the species Alchornea castaneaefolia Willd. A. Juss. and Alchornea glandulosa Poepp. & Endl. are used by the local population to treat rheumatism, arthritis and muscular pains. In view of the popular use of these plants as medicines and the potential risks from their consumption, we assessed the mutagenic potential of chloroform and methanol extracts of the leaves of these plant species, employing the in vivo micronucleus test and the Ames assay. The data obtained showed that the chloroform extracts were not mutagenic. The methanol extract of A. castaneaefolia was mutagenic to strain TA98 of Salmonella typhimurium and the methanol extract of A. glandulosa to strains TA98 and TA97a. The methanol extracts of both species of Alchornea were mutagenic in vivo at the largest dose employed. The probable mutagenic agents involved were the aglycone quercetin and amentoflavone, present in both species.