Psilostachyin C: a natural compound with trypanocidal activity

Sülsen, Valeria P.; Frank, Fernanda M.; Cazorla, Silvia I.; Barrera, Patricia; Freixa, Blanca; Vila, Roser; Sosa, Miguel A. Gama; Malchiodi, Emilio L.; Muschietti, Liliana; Martino, Virginia

doi:10.1016/j.ijantimicag.2011.02.003

Cited by 42 publications

(37 citation statements)

References 32 publications

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“…Extraction of the aerial parts of A. elatior and A. scabra was done by maceration with dichloromethane∶methanol (1∶1), as previously described [22].…”

Section: Methodsmentioning

confidence: 99%

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Natural Terpenoids from Ambrosia Species Are Active In Vitro and In Vivo against Human Pathogenic Trypanosomatids

et al. 2013

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Among the natural compounds, terpenoids play an important role in the drug discovery process for tropical diseases. The aim of the present work was to isolate antiprotozoal compounds from Ambrosia elatior and A. scabra. The sesquiterpene lactone (STL) cumanin was isolated from A. elatior whereas two other STLs, psilostachyin and cordilin, and one sterol glycoside, daucosterol, were isolated from A. scabra. Cumanin and cordilin were active against Trypanosoma cruzi epimastigotes showing 50% inhibition concentrations (IC50) values of 12 µM and 26 µM, respectively. Moreover, these compounds are active against bloodstrean trypomastigotes, regardless of the T. cruzi strain tested. Psilostachyin and cumanin were also active against amastigote forms with IC50 values of 21 µM and 8 µM, respectively. By contrast, daucosterol showed moderate activity on epimastigotes and trypomastigotes and was inactive against amastigote forms. We also found that cumanin and psilostachyin exhibited an additive effect in their trypanocidal activity when these two drugs were tested together. Cumanin has leishmanicidal activity with growth inhibition values greater than 80% at a concentration of 5 µg/ml (19 µM), against both L. braziliensis and L. amazonensis promastigotes. In an in vivo model of T. cruzi infection, cumanin was more active than benznidazole, producing an 8-fold reduction in parasitemia levels during the acute phase of the infection compared with the control group, and more importantly, a reduction in mortality with 66% of the animals surviving, in comparison with 100% mortality in the control group. Cumanin also showed nontoxic effects at the doses assayed in vivo, as determined using markers of hepatic damage.

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“…Extraction of the aerial parts of A. elatior and A. scabra was done by maceration with dichloromethane∶methanol (1∶1), as previously described [22].…”

Section: Methodsmentioning

confidence: 99%

“…Vero cells were assayed to determine viability by the MTT method [22]. Cells (5×10 5 ) were settled at a final volume of 150 µl in a flat-bottom 96-well microplate and were cultured at 37°C in a 5% CO 2 atmosphere in the absence or presence of increasing concentrations of the pure compounds.…”

Section: Methodsmentioning

confidence: 99%

Natural Terpenoids from Ambrosia Species Are Active In Vitro and In Vivo against Human Pathogenic Trypanosomatids

et al. 2013

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“…The trypanocidal effects were also tested on bloodstream trypomastigotes according to a standard WHO protocol with minor modifications (20,21). Briefly, parasites were counted in a Neubauer chamber and the blood was diluted in RPMI culture medium to a final concentration of 1.5 ϫ 10 6 trypomastigotes/ml.…”

Section: Methodsmentioning

confidence: 99%

Antiparasitic Effect of Vitamin B ₁₂ on Trypanosoma cruzi

Ciccarelli

Frank

Puente

et al. 2012

Antimicrob Agents Chemother

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A nutritional characteristic of trypanosomatid protozoa is that they need a heme compound as a growth factor. Because of the cytotoxic activity of heme and its structural similarity to cobalamins, we have investigated the in vitro and in vivo effect of vitamin B 12 (or cyanocobalamin) on the different forms of Trypanosoma cruzi. Cyanocobalamin showed a marked antiparasitic activity against epimastigotes (50% inhibitory concentration [IC 50 ], 2.42 M), amastigotes (IC 50 , 10.69 M), and trypomastigotes (IC 50 , 9.46 M). Anti-epimastigote and -trypomastigote values were 1.7 to 4 times lower than those obtained with the reference drug benznidazole (Bnz). We also found that B 12 and hemin do not interact with each other in their modes of action. Our results show that B 12 increases intracellular oxidative activity and stimulates both superoxide dismutase (50%) and ascorbate peroxidase (20%) activities, while the activity of trypanothione reductase was not modified. In addition, we found that the antioxidants dithiothreitol and ascorbic acid increase the susceptibility of the parasite to the cytotoxic action of B 12 . We propose that vitamin B 12 exerts its growth-inhibitory effect through the generation of reactive oxygen species. In an in vivo assay, a significant reduction in the number of circulating parasites was found in T. cruzi-infected mice treated with cyanocobalamin and ascorbic acid. The reduction of parasitemia in benznidazole-treated mice was improved by the addition of these vitamins. According to our results, a combination of B 12 and Bnz should be further investigated due to its potential as a new therapeutic modality for the treatment of Chagas' disease.

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“…Vero cells were employed to determine the viability by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) method (Sülsen et al 2011). Cells (5 Â 10 5 ) were settled at a final volume of 150 mL in a flat-bottom 96-well microplate and were cultured at 37 C in a 5% CO 2 atmosphere in the absence or presence of increasing concentrations of the pure compounds 1 and 3 (12.5-500 mg/mL).…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Trypanocidal and leishmanicidal activities of flavonoids isolated fromStevia satureiifoliavar.satureiifolia

Beer

Frank

Elso

et al. 2016

Pharmaceutical Biology

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Context Chagas' disease and leishmaniasis produce significant disability and mortality with great social and economic impact. The genus Stevia (Asteraceae) is a potential source of antiprotozoal compounds.Objective Aerial parts of four Stevia species were screened on Trypanosoma cruzi. Stevia satureiifolia (Lam.) Sch. Bip. var. satureiifolia (Asteraceae) dichloromethane extract was selected for a bioassay-guided fractionation in order to isolate its active compounds. Additionally, the antileishmanial activity and the cytotoxicity of these compounds on mammalian cells were assessed. Materials and methodsThe dichloromethane extract was fractionated by column chromatography. The isolated compounds were evaluated using concentrations of 0-100 mg/mL on T. cruzi epimastigotes and on Leishmania braziliensis promastigotes for 72 h, on trypomastigotes and amastigotes of T. cruzi for 24 h and 120 h, respectively. The compounds' cytotoxicity (12.5-500 mg/mL) was assessed on Vero cells by the MTT assay. The structure elucidation of each compound was performed by spectroscopic methods and HPLC analysis.Results The dichloromethane extracts of Stevia species showed significant activity on T. cruzi epimastigotes. The flavonoids eupatorin (1.3%), cirsimaritin (1.9%) and 5-desmethylsinensetin (1.5%) were isolated from S. satureiifolia var. satureiifolia extract. Eupatorin and 5-desmethylsinensetin showed IC 50 values of 0.2 and 0.4 mg/mL on T. cruzi epimastigotes and 61.8 and 75.1 mg/mL on trypomastigotes, respectively. The flavonoid 5-desmethylsinensetin showed moderate activity against T. cruzi amastigotes (IC 50 value ¼ 78.7 mg/mL) and was the most active compound on L. braziliensis promastigotes (IC 50 value ¼ 37.0 mg/mL). Neither of the flavonoids showed cytotoxicity on Vero cells, up to a concentration of 500 mg/mL. ARTICLE HISTORY

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Psilostachyin C: a natural compound with trypanocidal activity

Cited by 42 publications

References 32 publications

Natural Terpenoids from Ambrosia Species Are Active In Vitro and In Vivo against Human Pathogenic Trypanosomatids

Natural Terpenoids from Ambrosia Species Are Active In Vitro and In Vivo against Human Pathogenic Trypanosomatids

Antiparasitic Effect of Vitamin B ₁₂ on Trypanosoma cruzi

Trypanocidal and leishmanicidal activities of flavonoids isolated fromStevia satureiifoliavar.satureiifolia

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Psilostachyin C: a natural compound with trypanocidal activity

Cited by 42 publications

References 32 publications

Natural Terpenoids from Ambrosia Species Are Active In Vitro and In Vivo against Human Pathogenic Trypanosomatids

Natural Terpenoids from Ambrosia Species Are Active In Vitro and In Vivo against Human Pathogenic Trypanosomatids

Antiparasitic Effect of Vitamin B 12 on Trypanosoma cruzi

Trypanocidal and leishmanicidal activities of flavonoids isolated fromStevia satureiifoliavar.satureiifolia

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Antiparasitic Effect of Vitamin B ₁₂ on Trypanosoma cruzi