BACKGROUND: The current drugs for Chagas disease treatment present several limitations. METHODS: 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.
BACKGROUND: The current drugs for Chagas disease treatment present several limitations. METHODS: The sesquiterpene lactonegoyazensolide (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 miceinfected 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.
Entities:
Keywords:
Goyazensolide; Trypanosoma cruzi; in vitro; in vivo; toxicity; treatment
Authors: Orlando G Elso; Augusto E Bivona; Andrés Sanchez Alberti; Natacha Cerny; Lucas Fabian; Celina Morales; César A N Catalán; Emilio L Malchiodi; Silvia I Cazorla; Valeria P Sülsen Journal: Molecules Date: 2020-04-25 Impact factor: 4.411
Authors: Andrés Sánchez Alberti; María F Beer; Natacha Cerny; Augusto E Bivona; Lucas Fabian; Celina Morales; Albertina Moglioni; Emilio L Malchiodi; Osvaldo J Donadel; Valeria P Sülsen Journal: ACS Omega Date: 2021-12-20