Proteinase Inhibitors: A Promising Drug Class for Treating Leishmaniasis

Abstract

This review presents and discusses the current status and perspectives of leishmaniasis treatment, with a special focus on the use of proteinase inhibitors. The history of treatment development, the first- and second-choice modern drugs and the advantages and disadvantages of using proteinases inhibitors as leishmanicidal treatments are presented and discussed. The reports gathered herein confirm the potential usefulness of proteinases inhibitors as an alternative or complement to the current leishmaniasis treatments. They also support the hypothesis that a combined treatment with multiple proteinase inhibitors may be efficient against Leishmania infections in vertebrate hosts.

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

“…The current treatment, based on pentavalent antimony, is associated with severe side effects, such as pain, gastrointestinal disorders, headache, anorexia, and cardiac, hepatic, and pancreatic toxicity (33). For this reason, the development of new chemotherapeutic agents, potentially including plant-derived compounds such as the naphthoquinones, is required (10,11).…”

Recent updates and perspectives on leishmaniasis

“…Also, peptidases (proteases) are enzymes that are considered interesting targets for chemotherapy [31,41]. The only aspartic protease present in leishmaniae belongs to the family of the A2 retrovirallike aspartic proteases and is inhibited by drugs originally developed as inhibitors of HIV protease [42,43].…”

Why strategies to control Leishmania spp. multiplication based on the use of proteinase inhibitors should consider multiple targets and not only a single enzyme

“…As the current chemotherapy options for these diseases are not entirely efficient and resistant strains are emerging, other components of the parasite have been proposed as potential targets to control the cutaneous or visceral infections; and, one such target are the proteinases [3].…”

“…Nevertheless, classical and novel proteinase inhibitors have been assayed continuously in parasite cultures or in experimental infection models to assess their potential antileishmanial effect [3]. Some of the assayed proteinase inhibitors that could be potentially used to develop therapies are listed in Table 1.…”