Emerging compounds and therapeutic strategies to treat infections from Trypanosoma brucei: an overhaul of the last 5-years patents

ABSTRACT

Introduction

Human African Trypanosomiasis is a neglected disease caused by infection from parasites belonging to the Trypanosoma brucei species. Only six drugs are currently available and employed depending on the stage of the infection: pentamidine, suramin, melarsoprol, eflornithine, nifurtimox, and fexinidazole. Joint research projects were launched in an attempt to find new therapeutic options for this severe and often lethal disease.

Areas covered

After a brief description of the recent literature on the parasite and the disease, we searched for patents dealing with the proposal of new antitrypanosomiasis agents and, following the PRISMA guidelines, we filtered the results to those published from 2018 onwards returning suitable entries, which represent the contemporary landscape of compounds/strategies against Trypanosoma brucei. In addition, some relevant publications from the overall scientific literature were also discussed.

Expert opinion

This review comprehensively covers and analyzes the most recent advances not only in the discovery of new inhibitors and their structure–activity relationships but also in the assessment of innovative biological targets opening new scenarios in the MedChem field. Finally, also new vaccines and formulations recently patented were described. However, natural and synthetic compounds were analyzed in terms of inhibitory activity and selective toxicity against human cells.

KEYWORDS:

• Trypanosoma brucei
• cysteine protease
• inhibitors
• dihydrofolate reductase
• pterine reductase 1
• oxaborole analogues
• fusaricidin A
• human African trypanosomiasis

Article highlights

• The current status of the anti-trypanosomal therapy was updated.

• New therapeutic targets in Trypanosoma brucei-related diseases emerged in the last 5 years.

• Newly synthesized molecules and naturally occurring bacterial metabolites were licensed as anti-T. brucei agents.

• Peptidomimetic drugs, aliphatic macrocycles, oxaborole analogues, and heterocycles are the most studied scaffolds in this field.

• Compounds were herein described in terms of inhibitory activity against the parasite’s infection and selective toxicity against human cells.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors contributions

F Melfi and E Haloci searched for the literature. C Campestre, A Ammazzalorso, and R Grande filtered the search results. All the authors analyzed the data. F Melfi, S Carradori, and I D’Agostino wrote the manuscript. All the authors read and approved the final version of the manuscript.

Additional information

Funding

This paper was not funded.