Dynamic covalent bonding (DCB): the bond lability of alkoxyamines as drugs against <i>Schistosoma mansoni</i> and <i>Plasmodium falciparum</i>
Dynamic covalent bonding (DCB) has been a rising concept for the past several years in materials sciences. This article describes how the bond lability involved in DCB is applied to develop drugs against tropical parasitic diseases such as malaria and bilharziasis. Recently, we showed that some alkoxyamines (typical molecules exhibiting DCB) exhibit <i>in vitro</i> activities against <i>S. mansoni</i> (for A8L, 100% worm mortality in 48 hours at 10 μg ml<sup>-1</sup>) and <i>P. falciparum</i> (for A8L, IC<sub>50</sub> = 270 nM). Here, the combination of enzymatic-physical (solvent effect) activation or of enzymatic-chemical (acetal hydrolysis) activation is used to develop alkoxyamines that show activity against both parasites. The enzymatic step controls the specificity of the drug.
Authors
- Jérôme Boissier (ORCID: https://orcid.org/0000-0002-0793-3108)
- Anne Robert (ORCID: https://orcid.org/0000-0002-9092-6776)
- Gérard Audran (ORCID: https://orcid.org/0000-0002-5679-3471)
- Françoise Benoit‐Vical (ORCID: https://orcid.org/0000-0002-9468-4823)
- Raphaël Bikanga
- Philippe Mellet (ORCID: https://orcid.org/0000-0001-5499-9735)
- Jean‐Michel Augereau (ORCID: https://orcid.org/0000-0002-2847-1969)
- Michel Nguyen (ORCID: https://orcid.org/0000-0002-6496-0495)
- Sylvain R. A. Marque (ORCID: https://orcid.org/0000-0002-3050-8468)
- Jean‐Patrick Joly (ORCID: https://orcid.org/0000-0002-4844-7499)
- Lucie Paloque (ORCID: https://orcid.org/0000-0003-0359-3959)
- Ange W. Embo-Ibouanga
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Université de Bordeaux (FR)
- Université de Perpignan (FR)
- Ifremer (FR)
- Inserm (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Aix-Marseille Université (FR)
- Institut de Chimie Radicalaire (FR)
- Institut de Pharmacologie et de Biologie Structurale (FR)
- Centre de Résonance Magnétique des Systèmes Biologiques (FR)
- Bordeaux Population Health (FR)
- Laboratoire de Chimie de Coordination (FR)
- Université des Sciences et Techniques de Masuku (GA)
Publication Details
- Journal
- Organic & Biomolecular Chemistry
- Published
- 2024-12-03
- DOI
- https://doi.org/10.1039/d4ob01644k
- Citations
- 1
- Primary Topic
- Chemical Reaction Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.25
Funders
- Aix-Marseille Université
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Centre National de la Recherche Scientifique