Effect of cumanin diacetate, a sesquiterpene lactone derivative, on an in vivo chronic model of Chagas disease

SANCHEZ ALBERTI A.; MALCHIODI E.; BEER MF.; BIVONA A.; CERNY N.; DONADEL O.; SULSEN V.

Congreso; Drug Discovery for Neglected Diseases International Congress 2018; 2018

Chagas' disease is a parasitic disease caused by the protozoan parasite Trypanosoma cruzi. It is considered, among others, a Neglected Tropical Disease. The drugs currently in use for the treatment of this parasitosis are not effective in chronic stages and have severe drawbacks.Natural products play an important role in the discovery and development of new drugs and mny natural compounds are used in current chemotherapy. Chemical modification of natural compounds is a strategy to enhance the activity and reduce toxic effects. lt is noteworthy that some semi­ synthetic compounds derived from a natural framework sometimes improve the biological activity respect the original natural product or enhance its biodisponibility. Sesquiterpene lactones (STLs) are a group of natural terpenoids with a wide range of biological activities being the antiparasitic one of the most important. The STL artemisinin and its semi-synthetic derivatives are used nowadays in combination therapies for the treatment of malaria.Cumanin diacetate (CumD), a derivative of the STL cumanin, isolated from Ambrosia tenuifolia (Asteraceae), was active and selective against Trypanosoma cruzi epimastigotes and tripomastigotes (IC50% of 3.2 and 32.4 µg/ml, respectively). Since CumD presented significant in vitro activity on the different T.cruzi stages and it was more selective with respect the natural compound cumanin, the aim of this study was to evaluate the effect of CumD and its combination with benznidazol in an in vivo chronic model of Chagas disease. Four groups of five Balb/c mice each were infected by intraperitoneal (IP) via with 300000 blood tripomastigotes (K98 strain). Between days 11 and 15 post infection the animals were treated IP with CumD, and CumD+benznidazol (1 mg/kg of body weight/day). As control, one group of mice (GI) received DMSO that was used as drug vehicle and as negative control; another group (GII) was treated with benznidazol as positive control Infected mice that received CumD presented a lower blood parasitemia, compared to GI, being the area under the curve 3.234 (*p