ArticleACS infectious diseases2019
Successful Aspects of the Coadministration of Sterol 14α-Demethylase Inhibitor VFV and Benznidazole in Experimental Mouse Models of Chagas Disease Caused by the Drug-Resistant Strain of Trypanosoma cruzi.
Article in ACS infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Advances and challenges in the search for new treatments for Chagas disease.Memorias do Instituto Oswaldo Cruz · 2026Review
- In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi.Memorias do Instituto Oswaldo Cruz · 2025Article
- 1,2,4-Oxadiazole Derivatives: Physicochemical Properties, Antileishmanial Potential, Docking and Molecular Dynamic Simulations ofMolecules (Basel, Switzerland) · 2024Article
- Drug screening and development cascade for Chagas disease: an update of in vitro and in vivo experimental models.Memorias do Instituto Oswaldo Cruz · 2024Review
- Arylimidamides Have Potential for Chemoprophylaxis against Blood-Transmitted Chagas Disease.Pathogens (Basel, Switzerland) · 2023Article
- Perspectives for a new drug candidate for Chagas disease therapy.Memorias do Instituto Oswaldo Cruz · 2022Article
- 7-Aryl-7-deazapurine 3'-deoxyribonucleoside derivative as a novel lead for Chagas' disease therapy:JAC-antimicrobial resistance · 2021Article
- Combination therapy using nitro compounds improves the efficacy of experimental Chagas disease treatment.Parasitology · 2021Article
- Article
- Review on Experimental Treatment Strategies AgainstJournal of experimental pharmacology · 2021Review
- Activity profile of two 5-nitroindazole derivatives over the moderately drug-resistantParasitology · 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
- Current trends in the pharmacological management of Chagas disease.International journal for parasitology. Drugs and drug resistance · 2020Review
- Advances in preclinical approaches to Chagas disease drug discovery.Expert opinion on drug discovery · 2019Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Up to now, no vaccines are available for Chagas disease, and the current therapy is largely unsatisfactory. Novel imidazole-based scaffolds of protozoan sterol 14α-demethylase (CYP51) inhibitors have demonstrated potent antiparasitic activity with no acute toxicity. Presently our aim was to investigate the effectiveness of the experimental 14α-demethylase inhibitor VFV in the mouse models of Trypanosoma cruzi infection using a naturally drug-resistant Colombiana strain, under monotherapy and in association with the reference drug, benznidazole (Bz). The treatment with VFV resulted in complete parasitemia suppression and 100% animal survival when administered orally (given in 10% DMSO plus 5% Arabic gum) at 25 mg/kg (bid) for 60 days. However, as parasite relapse was found using VFV alone under this treatment scheme, the coadministration of VFV with Bz was assayed giving simultaneously (for 60 days, bid) by oral route, under two different drug vehicles (10% DMSO plus 5% Gum Arabic with or without 3% Tween 80). All tested mice groups resulted in >99.9% of parasitemia decrease and 100% animal survival. qPCR analysis performed on cyclophosphamide immunosuppressed mice revealed that, although presenting lack of cure, VFV given as monotherapy was 14-fold more active than Bz, and the coadministration of Bz plus VFV (given simultaneously, using 10% DMSO plus 5% Gum Arabic as vehicle) resulted in 106-fold lower blood parasitism as compared to the monotherapy of Bz. Another interesting finding was the parasitological cure in 70% of the animals treated with Bz and VFV when the coadministration was given using the VFV suspension in 10% DMSO + Arabic gum + Tween 80 (a formulation that we have found to provide a better pharmacokinetics), even after immunosuppression using cyclophosphamide cycles, supporting the promising aspect of the drug coadministration in improving the efficacy of therapeutic arsenal against T. cruzi.
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