| Full text | |
| Author(s): Show less - |
Pandey, Ramendra P.
;
Nascimento, Marilda Savoia
;
Franco, Caio Haddad
;
Bortoluci, Karina
;
Silva, Marcelo Nunes
;
Zingales, Bianca
;
Gibaldi, Daniel
;
Barrios, Leda Castano
;
Lannes-Vieira, Joseli
;
Cariste, Leonardo Moro
;
Vasconcelos, Jose Ronnie
;
Moraes, Carolina Borsoi
;
Freitas-Junior, Lucio H.
;
Kalil, Jorge
;
Alcantara, Laura
;
Cunha-Neto, Edecio
Total Authors: 16
|
| Document type: | Journal article |
| Source: | Antimicrobial Agents and Chemotherapy; v. 66, n. 11, p. 17-pg., 2022-10-31. |
| Abstract | |
Drug combinations and drug repurposing have emerged as promising strategies to develop novel treatments for infectious diseases, including Chagas disease. In this study, we aimed to investigate whether the repurposed drugs chloroquine (CQ) and colchicine (COL), known to inhibit Trypanosoma cruzi infection in host cells, could boost the anti-T. cruzi effect of the trypanocidal drug benznidazole (BZN), increasing its therapeutic efficacy while reducing the dose needed to eradicate the parasite. The combination of BZN and COL exhibited cytotoxicity to infected cells and low antiparasitic activity. Conversely, a combination of BZN and CQ significantly reduced T. cruzi infection in vitro, with no apparent cytotoxicity. This effect seemed to be consistent across different cell lines and against both the partially BZN-resistant Y and the highly BZN-resistant Colombiana strains. In vivo experiments in an acute murine model showed that the BZN+CQ combination was eight times more effective in reducing T. cruzi infection in the acute phase than BZN monotherapy. In summary, our results demonstrate that the concomitant administration of CQ and BZN potentiates the trypanocidal activity of BZN, leading to a reduction in the dose needed to achieve an effective response. In a translational context, it could represent a higher efficacy of treatment while also mitigating the adverse effects of high doses of BZN. Our study also reinforces the relevance of drug combination and repurposing approaches in the field of Chagas disease drug discovery. (AU) | |
| FAPESP's process: | 16/15209-0 - New therapies for Chagas Disease: repurposing of drugs acting on the invasion of host cells by T. cruzi, and potentiation of benznidazole effect in resistant strains and in the hamster model of chronic chagas disease cardiomyopathy |
| Grantee: | Edecio Cunha Neto |
| Support Opportunities: | Research Grants - Research in Public Policies for the National Health Care System (PP-SUS) |
| FAPESP's process: | 14/50708-2 - Effect of nanoparticles containing a drug combination targeting different steps of the T. cruzi cell invasion/replication on T. cruzi infection |
| Grantee: | Ramendra Pati Pandey |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |