title: Why calpain inhibitors are interesting leading compounds to search for new therapeutic options to treat leishmaniasis?
abstract: Leishmaniasis is a neglected disease, which needs improvements in drug development, mainly due to the toxicity, parasite resistance and low compliance of patients to treatment. Therefore, the development of new chemotherapeutic compounds is an urgent need. This opinion article will briefly highlight the feasible use of calpain inhibitors as leading compounds to search for new therapeutic options to treat leishmaniasis. The milestone of this approach is to take advantage on the myriad of inhibitors developed against calpains, some of which are in advanced clinical trials. The deregulated activity of these enzymes is associated with several pathologies, such as strokes, diabetes and Parkinson's disease, to name a few. In Leishmania, calpain upregulation has been associated to drug resistance and virulence. Whereas the difficulties in developing new drugs for neglected diseases are more economical than biotechnological, repurposing approach with compounds already approved for clinical use by the regulatory agencies can be an interesting shortcut to a successful chemotherapeutic treatment for leishmaniasis.
authors.affiliation: Laboratório de Estudos Integrados em Protozoologia,Instituto Oswaldo Cruz/FIOCRUZ,Rio de Janeiro,Brazil.
authors.forename: Vitor
authors.initials: V
authors.lastname: Ennes-Vidal
authors.affiliation: Laboratório de Biologia Celular,Instituto Oswaldo Cruz/FIOCRUZ,Rio de Janeiro,Brazil.
authors.forename: Rubem Figueiredo Sadock
authors.initials: RF
authors.lastname: Menna-Barreto
authors.affiliation: Laboratório de Investigação de Peptidases,Universidade Federal do Rio de Janeiro,Rio de Janeiro,Brazil.
authors.forename: Marta Helena
authors.initials: MH
authors.lastname: Branquinha
authors.affiliation: Laboratório de Investigação de Peptidases,Universidade Federal do Rio de Janeiro,Rio de Janeiro,Brazil.
authors.forename: André Luis Souza
authors.initials: AL
authors.lastname: Dos Santos
authors.affiliation: Laboratório de Estudos Integrados em Protozoologia,Instituto Oswaldo Cruz/FIOCRUZ,Rio de Janeiro,Brazil.
authors.forename: Claudia Masini
authors.initials: CM
authors.lastname: D'Avila-Levy
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D007891:Leishmania / Q000187:drug effects / Q000378:metabolism*; D007896:Leishmaniasis / Q000188:drug therapy*; D058069:Neglected Diseases / Q000188:drug therapy
chemical_list: D000981:Antiprotozoal Agents; D002154:Calpain
keywords: Calpain inhibitors; MDL28170; leishmaniasis; repurpose approach