ArticlePloS one2011
Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Novel amidines and analogues as promising agents against intracellular parasites: a systematic review.Parasitology · 2013Pooled it
- Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial.The Lancet. Infectious diseases · 2018Trial
- Sequential combined treatment with allopurinol and benznidazole in the chronic phase of Trypanosoma cruzi infection: a pilot study.The Journal of antimicrobial chemotherapy · 2013Trial
- Short-course combination treatment for experimental chronic Chagas disease.Science translational medicine · 2023Article
- Arylimidamides Have Potential for Chemoprophylaxis against Blood-Transmitted Chagas Disease.Pathogens (Basel, Switzerland) · 2023Article
- Functionalized Nitroimidazole Scaffold Construction and Their Pharmaceutical Applications: A 1950-2021 Comprehensive Overview.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review on Experimental Treatment Strategies AgainstJournal of experimental pharmacology · 2021Review
- Combination With Tomatidine Improves the Potency of Posaconazole AgainstFrontiers in cellular and infection microbiology · 2021Article
- Efficacy of Novel Pyrazolone Phosphodiesterase Inhibitors in Experimental Mouse Models of Trypanosoma cruzi.Antimicrobial agents and chemotherapy · 2020Article
- Combination Therapy Using Benznidazole and Aspirin during the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic Phase.Antimicrobial agents and chemotherapy · 2020Article
- Efficacy of the Benznidazole+Posaconazole combination therapy in parasitemia reduction: An experimental murine model of acute Chagas.Revista da Sociedade Brasileira de Medicina Tropical · 2020Article
- In vitro drug susceptibility of two strains of the wildlife trypanosome, Trypanosoma copemani: A comparison with Trypanosoma cruzi.International journal for parasitology. Drugs and drug resistance · 2017Article
- In Vitro and In Vivo Trypanosomicidal Action of Novel Arylimidamides against Trypanosoma cruzi.Antimicrobial agents and chemotherapy · 2016Article
- Benznidazole and posaconazole in experimental Chagas disease: positive interaction in concomitant and sequential treatments.PLoS neglected tropical diseases · 2013Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activity of benznidazole (Bz) in combination with the diamidine prodrug DB289 and in combination with the arylimidamide DB766 upon T. cruzi infection in vivo. The oral treatment of T.cruzi-infected mice with DB289 and Benznidazole (Bz) alone reduced the number of circulating parasites compared with untreated mice by about 70% and 90%, respectively. However, the combination of these two compounds decreased the parasitemia by 99% and protected against animal mortality by 100%, but without providing a parasitological cure. When Bz (p.o) was combined with DB766 (via i.p. route), at least a 99.5% decrease in parasitemia levels was observed. DB766+Bz also provided 100% protection against mice mortality while Bz alone provided about 87% protection. This combined therapy also reduced the tissular lesions induced by T. cruzi infection: Bz alone reduced GPT and CK plasma levels by about 12% and 78% compared to untreated mice group, the combination of Bz with DB766 resulted in a reduction of GPT and CK plasma levels of 56% and 91%. Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals.
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Registered trials
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