https://orcid.org/0000-0002-1277-7728
Abstract
Neglected tropical diseases (NTDs) pose a major threat in tropical zones for impoverished populations. Difficulty of access, adverse effects or low efficacy limit the use of current therapeutic options. Therefore, development of new drugs against NTDs is a necessity. Compounds containing an aminopyridine (AP) moiety are of great interest for the design of new anti-NTD drugs due to their intrinsic properties compared with their closest chemical structures. Currently, over 40 compounds with an AP moiety are on the market, but none is used against NTDs despite active research on APs. The aim of this review is to present the medicinal chemistry work carried out with these scaffolds, against protozoan NTDs: Trypanosoma cruzi, Trypanosoma brucei or Leishmania spp.
GRAPHICAL ABSTRACT
Introduction
Neglected Tropical Diseases (NTDs) are major threat to impoverished populations in tropical zones due to the lack of adverse-free efficient oral treatments.
Aminopyridines compounds active against Trypanosoma cruzi, Trypanosoma brucei & Leishmania spp.
Because of their intrinsic properties and ease of introduction into molecules, aminopyridines (APs) are interesting scaffolds for the development of new anti-NTD drugs.
The work presented focuses on the development of AP drugs targeting Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp.
APs got three main contributions to the compounds in which they are included: lipophilicity reduction, additional(s) target interaction(s) and intermediate structure allowing access to more complex aza–heterocycles (such as pyrimidines or imidazoles).
Conclusion
APs should be further included in drug discovery work focused on anti-NTD drugs because of their possible positive outcome on aqueous solubility and metabolic stability.
Supplementary material
Supplementary data for this article can be accessed at https://doi.org/10.1080/17568919.2024.2359361
Author contributions
Writing – review: R Mustière, A Dassonville-Klimpt, P Sonnet. Project administration & editing: P Sonnet.
Financial disclosure
The authors have no 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.
Competing interests disclosure
The authors have no competing interests or relevant affiliations with any organization or entity 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.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.