Trypanocidal Flavonoids from <i>Trixis vauthieri</i>

Ribeiro, Antônia; Piló‐Veloso, Dorila; Romanha, Álvaro J.; Zani, Carlos L.

doi:10.1021/np970196p

Cited by 54 publications

(38 citation statements)

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“…There is a vast literature describing that natural products produced by plants, fungi and other organisms are the direct source of or inspiration for many of the currently available medicines (Newman & Cragg 2007). In this regard, our group screens the Brazilian biodiversity for new bioactive natural products using in vitro bioassays related to neglected diseases, especially Chagas disease and leishmaniasis (Ribeiro et al 1997, Rosa et al 2005. We evaluated more than 3,000 extracts from plant and fungi using an inhibition assay with trypanothione reductase (TR) (unpublished results).…”

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confidence: 99%

A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation

Cota

Rosa

Fagundes

et al. 2008

Mem. Inst. Oswaldo Cruz

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The fungus Lentinus strigosus (Pegler 1983) (Polyporaceae, basidiomycete) was selected in a screen for inhibitory activity on Trypanosoma cruzi trypanothione reductase (TR). The crude extract of L. strigosus was able to completely inhibit TR at 20 µg/ml. Two triquinane sesquiterpenoids (dihydrohypnophilin and hypnophilin), in addition to two panepoxydol derivatives (neopanepoxydol and panepoxydone), were isolated using a bioassay-guided fractionation protocol. Hypnophilin and panepoxydone displayed IC 50 values of 0.8 and 38.9 µM in the TR assay, respectively, while the other two compounds were inactive. The activity of hypnophilin was confirmed in a secondary assay with the intracellular amastigote forms of T. cruzi, in which it presented an IC 50 value of 2.5 µM. Quantitative flow cytometry experiments demonstrated that hypnophilin at 4 µM also reduced the proliferation of human peripheral blood monocluear cells (PBMC) stimulated with phytohemaglutinin, without any apparent interference on the viability of lymphocytes and monocytes. As the host immune response plays a pivotal role in the adverse events triggered by antigen release during treatment with trypanocidal drugs, the ability of hypnophilin to kill the intracellular forms of T. cruzi while modulating human PBMC proliferation suggests that this terpenoid may be a promising prototype for the development of new chemotherapeutical agents for Chagas disease. Key words: fungal natural products -Chagas disease -drug discovery -immunomodulators -BasidiomycotaChagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects millions of people in Latin America, having an enormous economic and social impact in the endemic areas. These patients rely on treatment with nitrofuran (nifurtimox; Bayer) or nitroimidazol (benznidazole; Roche), medicines that display little or no activity in chronic infections, in spite of their beneficial effect during the acute phase of the disease (Cançado 2002, Coura & Castro 2002. However, significant differences in the therapeutic effectiveness are observed between these two drugs, especially when considering distinct geographical areas, which is probably due to the occurrence of naturally resistant and susceptible T. cruzi strains (Filardi & Brener 1987, Toledo et al. 2003. Furthermore, both drugs cause several side effects that contribute to their reduced use in clinical medicine (Cançado 1985). Thus, new compounds are needed to develop more effective medicines to treat Chagas disease, espe- cially in its chronic phase, is needed (Schmidt & KrauthSiegel 2002, Nwaka & Ridley 2003. However, due to low profit prospects, the development of new trypanocidal drugs is not attractive to the pharmaceutical industry (Nwaka & Ridley 2003). Thus, this endeavor is being conducted mainly in academic laboratories (Fairlamb 1999).Among the many different strategies for drug discovery, screening the local biodiversity for bioactive natural products using appropriate bioassays is an interesting alternative for researchers in affec...

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confidence: 99%

A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation

Cota

Rosa

Fagundes

et al. 2008

Mem. Inst. Oswaldo Cruz

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“…They showed that these flavonoids, isolated from an active fraction of Conchocarpus heterophyllus (Rutaceae), presented low activity against trypomastigote forms of T. cruzi (IC 50 = 2116 and 787 µg/mL or 9531 and 1084 µmol/L, respectively) when compared with other flavonoids (Ribeiro et al, 1997;Ambrozin et al, 2004). Probably, the relevant activity obtained from the extract CFBH can be related to other characteristic metabolites of C. fruticosa.…”

Section: Resultsmentioning

confidence: 99%

Trypanocidal activity of flavonoids and limonoids isolated from Myrsinaceae and Meliaceae active plant extracts

Leite¹,

Neto²,

Ambrozin³

et al. 2010

Rev. bras. farmacogn.

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RESUMO: "Atividade tripanocida de flavonoides e limonoides isolados de extratos ativos de plantas de Myrsinaceae e Meliaceae". A atividade de extratos brutos de três espécies de Rapanea (Myrsinaceae) e de Cipadessa fruticosa (Meliaceae) foi avaliada in vitro contra formas tripomastigotas de Trypanosoma cruzi. Foram obtidos 33 extratos de diferentes órgãos das espécies estudadas, sendo que onze deles apresentaram atividades significantes (% de lise > 50) nos ensaios realizados. O fracionamento de um extrato ativo dos galhos de R. lancifolia (99,5%) resultou no isolamento de dois flavonoides (quercetina e taxifolina), que apresentaram baixa atividade tripanocida. De um extrato ativo dos frutos de C. fruticosa (97,7%) foram isolados os limonoides mexicanolídeos cipadesina, mexicanolídeo, febrifugina e cipadesina A, que foram moderadamente ativos sobre T. cruzi. Além disso, outros dois flavonoides (flavona e 7-metoxiflavona), previamente ensaiados contra T. cruzi, foram isolados do extrato hexânico dos galhos de C. fruticosa (100%). Os resultados obtidos aqui sugerem que as plantas avaliadas podem constituir fontes de novas substâncias ativas sobre o T. cruzi.Unitermos: Myrsinaceae, Meliaceae, atividade tripanocida, flavonoides, limonoides. ABSTRACT:The activity of crude extracts of three Rapanea species (Myrsinaceae) and Cipadessa fruticosa (Meliaceae) was evaluated in vitro against the trypomastigote forms of Trypanosoma cruzi. Thirty-three extracts from different organs of these species were assayed and eleven of them showed significant activity (lysis % >50). The fractionation of an active extract from branches of R. lancifolia (99.5%) led to the isolation of two flavonoids: quercetin and taxifolin, which have weak trypanocidal activity. Additionally, one active extract from fruits of C. fruticosa (97.7%) afforded mexicanolide limonoids: cipadesin, mexicanolide, febrifugin and cipadesin A, that were slightly active on T. cruzi. Moreover, other two flavonoids (flavone and 7-methoxyflavone), previously assayed against T. cruzi, were isolated from the hexane extract from branches of C. fruticosa (100%). The results presented here suggest that the plants evaluated could be a source of new active compounds against T. cruzi.

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“…According to Ribeiro et al (1997), sakuranetin (5) isolated from leaves of Trixis vauthieri L. killed 100% of trypomastigote forms of T. cruzi Y strain in vitro, at 100 µg mL -1 . In another report, this flavanone isolated from Baccharis retusa showed in vitro activity against T. cruzi trypomastigotes (IC 50 20.2 µg mL -1 ) (Grecco et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Oleanonic acid from Lippia lupulina (Verbenaceae) shows strong in vitro antileishmanial and antitrypanosomal activity

et al. 2016

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Leishmaniasis and Chagas disease affect millions of people in tropical and subtropical regions. Drugs used currently to treat such diseases often present undesirable side effects and low efficiency. The aim of this work was to identify extracts and isolated compounds from the genus Lippia with leishmanicidal and trypanocidal activity. , respectively). The triterpenoid oleanonic acid showed the strongest activity against these protozoans (IC 50 of 18.5 and 29.9 µM, respectively). Our results indicate that Lippia plants and their derivatives deserve further investigation in the search for new antiprotozoal drugs, particularly for the treatment of leishmaniasis and Chagas disease. KEYWORDS: Leishmanicidal, trypanocidal, triterpenoids, flavonoids, T. cruzi Ácido oleanônico isolado de Lippia lupulina (Verbenaceae) apresenta potentes atividades leishmanicida e tripanocida Leishmaniose e doença de Chagas afetam milhões de pessoas em regiões tropicais e subtropicais. As drogas atualmente usadas para tratar estas doenças frequentemente apresentam efeitos colaterais indesejáveis e baixa eficiência. Este trabalho teve como objetivo encontrar extratos, frações e compostos isolados de espécies do gênero Lippia com atividades leishmanicida e tripanocida. Quinze extratos de diferentes partes de plantas do gênero Lippia, com composições químicas parcialmente conhecidas, quatro frações de partição, seis substâncias e uma mistura de quatro flavanonas interconversíveis isolados de Lippia salviaefolia e Lippia lupulina foram testados, in vitro, frente a formas epimastigotas de Trypanosoma cruzi e promastigotas de Leishmania amazonensis. O extrato etanólico das raízes de L. lupulina apresentou atividade potente contra T. cruzi e L. amazonensis (IC 50 de 20,0 e 54,5 µg mL -1 , respectivamente), enquanto que o ácido oleanônico mostrou as atividades mais fortes contra estes protozoários, com IC 50 de 18,5 e 29,9 µM, respectivamente. Estes resultados indicam que espécies do gênero Lippia e seus derivados merecem investigações adicionais na busca por novas terapias antiprotozoárias, especialmente para o tratamento de leishmaniose e doença de Chagas.

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Trypanocidal Flavonoids from Trixis vauthieri

Cited by 54 publications

References 22 publications

A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation

A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation

Trypanocidal activity of flavonoids and limonoids isolated from Myrsinaceae and Meliaceae active plant extracts

Oleanonic acid from Lippia lupulina (Verbenaceae) shows strong in vitro antileishmanial and antitrypanosomal activity

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