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

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 calciumdependent 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.

Differences in Charge Distribution in Leishmania tarentolae Leishmanolysin Result in a Reduced Enzymatic Activity

“…Neglected diseases are a major public health problem in developing countries, including Brazil [1]. In the case of leishmaniasis, there are currently 12 million infected 2 of 16 people worldwide, with an estimation of 700,000 to 1 million new cases occurring per year and 350 million people living at risk of infection [2].…”