Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 117 | 2022
Perspective

Proteolytic inhibitors as alternative medicines to treat trypanosomatid-caused diseases: experience with calpain inhibitors

Vítor Ennes-Vidal1,+, André Luis Souza dos Santos2,3, Marta Helena Branquinha2, Claudia Masini d’Avila-Levy1

1Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Estudos Integrados em Protozoologia, Rio de Janeiro, RJ, Brasil
2Universidade Federal do Rio de Janeiro, Instituto de Microbiologia Paulo de Góes, Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Rio de Janeiro, RJ, Brasil
3Universidade Federal do Rio de Janeiro, Instituto de Química, Programa de Pós-Graduação em Bioquímica, Rio de Janeiro, RJ, Brasil

DOI: 10.1590/0074-02760220017
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ABSTRACT

The treatment for tropical neglected diseases, such as Chagas disease (CD) and leishmaniasis, is extremely limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures due to the parasite resistance. Consequently, there is urgency for the development of new therapeutic options to treat such diseases. Since peptidases from these parasites are responsible for crucial functions in their biology, these molecules have been explored as alternative targets. In this context, a myriad of proteolytic inhibitors has been developed against calcium-dependent cysteine-type peptidases, collectively called calpains, which are implicated in several human pathophysiological diseases. These molecules are highly expanded in the genome of trypanosomatids and they have been reported participating in several parasite biological processes. In the present perspective, we discuss our almost two decades of experience employing the calpain inhibitors as an interesting shortcut to a possible repurpose strategy to treat CD and leishmaniasis.

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Financial support: CNPq, FAPERJ, CAPES (Financial code - 001), FIOCRUZ.
+ Corresponding author: vidal@ioc.fiocruz.br
ORCID https://orcid.org/0000-0001-6122-1956
Received 17 January 2022
Accepted 28 January 2022

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