Please use this identifier to cite or link to this item:
Title: Amlodipine increases the therapeutic potential of ravuconazole upon Trypanosoma cruzi infection.
Authors: Machado, Yara Almeida
Bahia, Maria Terezinha
Caldas, Ivo Santana
Mazzeti, Ana Lia
Novaes, Rômulo Dias
Vilas Boas, Breno Raimundo
Santos, Lorena Júnia de Souza
Martins Filho, Olindo Assis
Marques, Marcos José
Diniz, Lívia de Figueiredo
Keywords: Chagas disease
Calcium channel blockers
Combination therapy
Experimental chemotherapy
Issue Date: 2020
Citation: MACHADO, Y. A. et al. Amlodipine increases the therapeutic potential of ravuconazole upon Trypanosoma cruzi infection. Antimicrobial Agents and Chemotherapy, v. 64, p. e02497-e02519, ago. 2020. Disponível em: <>. Acesso em: 10 jun. 2021.
Abstract: Mining existing agents that enhance the therapeutic potential of ergosterol biosynthesis inhibitors (EBI) is a promising approach to improve Chagas disease chemotherapy. In this study, we evaluated the effect of ravuconazole, an EBI, combined with amlodipine, a calcium channel blocker, upon Trypanosoma cruzi experimental infection. In vitro assays confirmed the trypanocidal activity of both compounds in monotherapy and demonstrated an additive effect (sum of the fractional inhibitory concentration [FIC] 0.5) of the combined treatment without additional toxicity to host cells. In vivo experiments, using a murine model of the T. cruzi Y strain in a short-term protocol, demonstrated that amlodipine, although lacking trypanocidal activity, dramatically increased the antiparasitic activity of underdosing ravuconazole regimens. Additional analysis using long-term treatment (20 days) showed that parasitemia relapse until 60 days after treatment was significatively lower in mice treated with the combination (4 out of 14 mice) than ravuconazole monotherapy (10 out of 14 mice), even in the presence of immunosuppressant pressure. Furthermore, the combined therapy was well tolerated and protected the mice from mortality. The treatments also impacted on the cellular and humoral immune response of infected animals, inducing a reduction of serum cytokine levels in all ravuconazole-treated mice. Our findings demonstrate that amlodipine is efficacious in enhancing the antiparasitic activity of ravuconazole in an experimental model of T. cruzi infection and indicates a potential strategy to be explored in Chagas disease treatment.
ISSN: 1098-6596
Appears in Collections:DECBI - Artigos publicados em periódicos

Files in This Item:
File Description SizeFormat 
  Restricted Access
956,2 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.