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Activities of Psilostachyin A and Cynaropicrin Against Trypanosoma Cruzi in Vitro and in Vivo

Activities of Psilostachyin A and Cynaropicrin Against Trypanosoma Cruzi in Vitro and in Vivo

Cristiane França da Silva, Denise da Gama Jaen Batista, Julianna Siciliano De Araújo, Marcos Meuser Batista, Jessica Lionel, Elen Mello de Souza, Erica Ripoll Hammer, Patricia Bernardino da Silva, Maria De Mieri, etc.

Antimicrob Agents Chemother. 2013 Nov;57(11):5307-14.

PMID: 23939901

Abstract:

In vitro and in vivo activities against Trypanosoma cruzi were evaluated for two sesquiterpene lactones: psilostachyin A and cynaropicrin. Cynaropicrin had previously been shown to potently inhibit African trypanosomes in vivo, and psilostachyin A had been reported to show in vivo effects against T. cruzi, albeit in another test design. In vitro data showed that cynaropicrin was more effective than psilostachyin A. Ultrastructural alterations induced by cynaropicrin included shedding events, detachment of large portions of the plasma membrane, and vesicular bodies and large vacuoles containing membranous structures, suggestive of parasite autophagy. Acute toxicity studies showed that one of two mice died at a cynaropicrin dose of 400 mg/kg of body weight given intraperitoneally (i.p.). Although no major plasma biochemical alterations could be detected, histopathology demonstrated that the liver was the most affected organ in cynaropicrin-treated animals. Although cynaropicrin was as effective as benznidazole against trypomastigotes in vitro, the treatment (once or twice a day) of T. cruzi-infected mice (up to 50 mg/kg/day cynaropicrin) did not suppress parasitemia or protect against mortality induced by the Y and Colombiana strains. Psilostachyin A (0.5 to 50 mg/kg/day given once a day) was not effective in the acute model of T. cruzi infection (Y strain), reaching 100% animal mortality. Our data demonstrate that although it is very promising against African trypanosomes, cynaropicrin does not show efficacy compared to benznidazole in acute mouse models of T. cruzi infection.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP35730780	Cynaropicrin		35730-78-0	Price

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