Activity of the sesquiterpene lactone goyazensolide against Trypanosoma cruzi in vitro and in vivo

Abstract

Background:The current drugs for Chagas disease treatment present several limitationsMethods:The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo.Results:The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL−1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg−1 day−1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg−1 day−1 by oral were negative in parasitological tests and survived.Conclusion:GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.

Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae Species

“…Eupatoriopicrin showed a potent effect, causing a greater decrease in the number of circulating parasites. Although reductions in the parasitaemia levels have been reported for others sesquiterpene lactones, scarce studies have investigated their performance to prevent tissue damages during the chronic phase of the parasite infection [25][26][27][28]. Importantly, we found that the treatment of infected animals with eupatoriopicrin was also effective to reduce the cardiac and mainly the skeletal damage associated to T. cruzi infection.…”

Plant Terpenoids as Hit Compounds against Trypanosomiasis

“…that displayed promising results against the intracellular amastigote form of T. cruzi (IC 50 = 0.181 µM/24 h, and IC 50 = 0.020 µM/48 h), showing a higher selectivity index than the positive control benznidazol (SI = 52.82 and 915.0 for 72 , at 24 h and 48 h, respectively, and SI = 4.85 and 41.0 for benznidazol, at 24 h and 48 h, respectively). Further in vivo assays were performed and 72 showed an important therapeutic activity in mice infected with T. cruzi , which was demonstrated by the high percentage of negative parasitological tests employed by the authors in the successive post-treatment evaluations [ 73 ].…”

Review on Experimental Treatment Strategies Against Trypanosoma cruzi

“…135 Sesquiterpene lactones have been demonstrating outstanding anti-T. cruzi activity. [136][137][138][139][140][141][142][143][144][145] They are isolated from a variety of species, mainly from the Asteraceae family. Lychnopholide 144 and goyazenzolide 145 are examples of potent sesquiterpene lactones, which showed high efficacy in T. cruzi-infected mice.…”

“…[136][137][138][139][140][141][142][143][144][145] They are isolated from a variety of species, mainly from the Asteraceae family. Lychnopholide 144 and goyazenzolide 145 are examples of potent sesquiterpene lactones, which showed high efficacy in T. cruzi-infected mice. Unfortunately, preclinical research involving natural products faces obstacles to translate their findings to clinical phases due to difficulties in isolating the active compound and dimensioning the batches, as well as difficulties in the standardization of the plant extracts following the different seasons.…”