Abstract
Peptide-based drugs are an attractive class of therapeutic agents, recently recognized by the pharmaceutical industry. These molecules are currently being used in the development of innovative therapies for diverse health conditions, including tropical diseases such as leishmaniasis. Despite its socioeconomic influence on public health, leishmaniasis remains long-neglected and categorized as a poverty-related disease, with limited treatment options. Peptides with antileishmanial effects encountered to date are a structurally heterogeneous group, which can be found in different natural sources—amphibians, reptiles, insects, bacteria, marine organisms, mammals, plants, and others—or inspired by natural toxins or proteins. This review details the biochemical and structural characteristics of over one hundred peptides and their potential use as molecular frameworks for the design of antileishmanial drug leads. Additionally, we detail the main chemical modifications or substitutions of amino acid residues carried out in the peptide sequence, and their implications in the development of antileishmanial candidates for clinical trials. Our bibliographic research highlights that the action of leishmanicidal peptides has been evaluated mainly using in vitro assays, with a special emphasis on the promastigote stage. In light of these findings, and considering the advances in the successful application of peptides in leishmaniasis chemotherapy, possible approaches and future directions are discussed here.
Highlights
L. tarentolae was modified to encode the human neutrophil peptide 1 (HNP-1) peptide sequence, taking advantage of the fact that L. tarentolae is not pathogenic and has long been considered an important model for the development of vaccines against leishmaniasis [14]. This species was found to be a highly effective HNP-1 secretor; BALB/c mice infected with L. major were injected with peptide-secreting L. tarentolae parasites
Several mechanisms and structural parameters have been proposed as underlying the action of peptides against Leishmania parasites, but they are mostly based on what is known about antimicrobial peptides in general, and lack specificity
Despite its overwhelming burden worldwide, leishmaniasis has attracted practically no interest from researchers aimed at developing adequate vaccines or drugs
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Resistance of Leishmania spp. parasites to the current conventional chemotherapy is increasing (susceptibility to available drugs is decreasing and is dependent on strains and isolates within the same species) [5,11,12], which is another relevant factor that threatens the adequate treatment of this disease [13]. In the case of antimicrobial peptides (AMP), mainly acting through pathogen membrane destabilization/disruption, they are less likely to select for resistant pathogen strains [17,18] Due to these peculiarities, peptide-based products have become interesting candidates for the design of an effective and safe treatment for leishmaniasis [19].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
