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American trypanosomiasis, or Chagas' disease, is caused by Trypanosoma cruzi and affects around 15 million people throughout the American continent. The available treatment is based on two nitroheterocyclic drugs, nifurtimox and benznidazole, both only partially effective and toxic. In this context, new drugs must be found. In our previous work, the tetrahydro-␤-carboline compound N-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-␤-carboline-3-carboxamide, named C4, showed a potent in vitro trypanocidal effect. The goal of this study was to evaluate the in vitro and in vivo trypanocidal effects of the compound C4 associated with other drugs (benznidazole, ketoconazole, and amphotericin B). For this, we used the checkerboard technique to analyze the effect of combinations of C4 reference drugs. C4 was assayed in a murine model alone as well as in association with benznidazole. We also evaluated the parasitemia, mortality, weight, and presence of amastigote nests in cardiac tissue. A synergic effect of C4 plus benznidazole against epimastigote and trypomastigote forms was observed in vitro, and in the murine model, we observed a substantial reduction in parasitemia levels and lowered mortality rates. These findings encourage supplementary investigations of carboline compounds as potential new trypanocidal drugs. C hagas' disease is an illness that affects around 15 million people on the American continent, and in Brazil, there are an estimated 3 million people infected with Trypanosoma cruzi, the causative agent of this disease (31).The currently available treatment is by two nitroheterocyclic drugs, nifurtimox and benznidazole (BZ), but both are unsatisfactory. Moreover, in Brazil, only BZ is available (19). In this context, new drugs or new therapeutic approaches must be developed. We recently reported that the tetrahydro-␤-carboline compound N-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-␤-carboline-3-carboxamide, named C4 (see Fig. 3), showed a strong in vitro trypanocidal effect (29).For the treatment of many infectious diseases, therapeutic associations are adopted, with very successful results. Previous works have shown the importance of combination therapy against several microorganisms such as bacteria (17,22,25), fungi (7,13,14), and protozoa such as Plasmodium (9, 21, 30), Leishmania (6, 16), and T. cruzi (3,20). In one of the few previous studies that reported synergistic activities of drugs for T. cruzi treatment, good synergistic activity between parthenolide and BZ was demonstrated (20).Therefore, based on the successful results of known therapeutic associations, the goal of this study was to evaluate the in vitro and in vivo trypanocidal activities of C4 associated with different reference drugs (BZ, ketoconazole, and amphotericin B). (ii) Checkerboard assay of effect of C4 on epimastigote and trypomastigote forms of Trypanosoma cruzi. For the checkerboard assay, we evaluated the trypanocidal effect of the compound C4 associated with other drugs (BZ, ketoconazole, and amphotericin B) on ep...

Recebido para publicação em 03/09/2013 Aceito para publicação em 28/05/2014 RESUMO. O fruto de noni (Morinda citrifolia L.) é consumido há milênios na medicina popular polinésia devido aos benefícios nutricionais e terapêuticos. O consumo de noni em outros países, incluindo o Brasil, cresceu vertiginosamente nos últimos anos em decorrência das atividades biológicas atribuídas a ingestão do suco da fruta, principalmente pela propriedade anticâncer. Contudo, a composição química da planta, que está relacionada com suas propriedades biológicas, é determinada pelo seu local de origem, e por influência do clima e do solo onde é cultivada. Neste sentido, este trabalho teve como objetivo analisar a polpa extraída de frutos maduros de noni cultivados em Maringá-PR. A análise da polpa in natura apresentou 89,16% ABSTRACT: Proximate composition, bioactive compounds and antioxidant activity of fruits of Morinda citrifolia L. (noni) cultivated in Paraná, Brazil. The noni fruit (Morinda citrifolia L.) has been consumed for millennia in the Polynesian folk medicine because of its nutritional and therapeutic benefits. The consumption of the noni fruit in other countries, including Brazil, has increased in recent years because of the biological activities attributed to the ingestion of noni juice, especially the anticancer effect. However, the chemical composition of the plant, which is related to its biological properties, is determined by its geographical origin and is influenced by climate and soil. Therefore, this study aimed to analyze the pulp extracted from noni fruit grown in Maringá, state of Paraná, Brazil. The fresh pulp analysis showed 89.16% of moisture, 0.75% of ash, 2.10% of protein, 2.19% of fat and 5.81% of carbohydrates. The bioactive compounds analyzed were anthocyanins (1.39 mg.100 g -1 pulp), yellow flavonoids (13.01 mg.100 g -1 pulp), carotenoids (0.45 mg.100 g -1 pulp) and vitamin C (12.16 mg.100 g -1 pulp). For the analysis of total phenols and antioxidant activity, different extracts were prepared. The highest total phenolic contents were found in the aqueous extract (1143.56 mg EAG.100 g -1 ), followed by the ethanol extract (966.96 mg EAG.100 g -1 ), methanol/acetone extract (820.88 mg EAG.100 g -1 ) and methanol extract (306.33 mg EAG.100 g -1 ). The results for the antioxidant capacity were determined by the EC 50 , which is concentration of extract required to reduce 50% of the DPPH radical. The best results for the antioxidant capacity were found in the methanol/ acetone extract (EC 50 of 25.18 mg.mL -1 ) and in the methanol extract (EC 50 of 25.96 mg.mL -1 ). The antioxidant activity of the fruit may be related to its vitamin C content, since the extracts with lower total phenolic content were those that had lower EC 50 values.

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The investigation of traditionally used medicinal plants is valuable both as a source of potential chemotherapeutic drugs and as a measure of safety for the continued use of these medicinal plants. Achillea millefolium L. (AM) is an ancient remedial herb native to Europe that is used to treat wounds, gastrointestinal and hepatobiliary disorders, inflammation, headaches, and pain. Bauhinia forficata Link (BF), an Asiatic plant, is one of the most commonly used plants in folk medicine against diabetes. The aim of this study was to evaluate the cytotoxic and antimutagenic potential of aqueous extracts of AM and BF on bone marrow cells of Wistar rats treated in vivo. These plant extracts possess considerable antioxidant activity due to the presence of flavonoids and phenolic compounds. These compounds were determinants to noncytotoxic and antimutagenic/protective action of these plants, that reduced statistically the percentage of chromosomal alterations induced by the chemotherapeutic agent cyclophosphamide in simultaneous (AM, 68%; BF, 91%), pre- (AM, 68%; BF, 71%), and post-treatment (AM, 67%; BF, 95%). Therefore, the results of this study indicate that extracts of A. millefolium and B. forficata have antimutagenic potential and that their consumption can benefit the health of those using them as an alternative therapy.

Leishmaniasis has an overwhelming impact on global public health especially in tropical and subtropical countries and the currently available antileishmanial drugs have serious side effects and low efficacy. Natural and synthetic compounds have been tested in the past few years against Leishmania and the beta-carboline class of compounds have shown great results in antiparasitic chemotherapy. In the present study, three 1-substituted beta-carboline-3-carboxamides (3-5) and 1-substituted beta-carboline-3-carboxylic acid (2) were synthesized and screened for in vitro activity against L. amazonensis. Compound 5 (N-benzyl 1-(4-methoxy)phenyl-9H-beta-carboline-3-carboxamide) had the best activity against promastigote and axenic amastigote forms with IC(50) of 2·6 and 1·0 μM, respectively. Its CC(50) on macrophages cell line was higher than 2457·0 μM with an SI ratio of 930·2. Against intracellular amastigote forms, it had a dose-dependent relationship with a 50% growth inhibitory concentration of 1·0 μM. Through morphological and ultrastructure analysis of promastigote forms treated with compound 5, alterations on cell shape and number of flagella and nuclear membrane damage were observed. For this, compound 5 supports the idea for more in vitro and in vivo studies.

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