Peptide-Alkoxyamine Drugs: An Innovative Approach to Fight Schistosomiasis: “Digging Their Graves with Their Forks” - Aix-Marseille Université Accéder directement au contenu
Article Dans Une Revue Pathogens Année : 2024

Peptide-Alkoxyamine Drugs: An Innovative Approach to Fight Schistosomiasis: “Digging Their Graves with Their Forks”

Michel Nguyen
Jean-Patrick Joly
Mathilde Coustets
  • Fonction : Auteur
Jean-Michel Augereau
Lucie Paloque
Nicolas Vanthuyne
Raphaël Bikanga
  • Fonction : Auteur
  • PersonId : 1397095
Anne Robert
Françoise Benoit-Vical
Gérard Audran
  • Fonction : Auteur
  • PersonId : 1077937
Philippe Mellet
  • Fonction : Auteur
  • PersonId : 1094325
Jérôme Boissier
Sylvain R A Marque
  • Fonction : Auteur
  • PersonId : 995795

Résumé

The expansion of drug resistant parasites sheds a serious concern on several neglected parasitic diseases. Our recent results on cancer led us to envision the use of peptide-alkoxyamines as a highly selective and efficient new drug against schistosome adult worms, the etiological agents of schistosomiasis. Indeed, the peptide tag of the hybrid compounds can be hydrolyzed by worm’s digestive enzymes to afford a highly labile alkoxyamine which homolyzes spontaneously and instantaneously into radicals—which are then used as a drug against Schistosome adult parasites. This approach is nicely summarized as digging their graves with their forks. Several hybrid peptide-alkoxyamines were prepared and clearly showed an activity: two of the tested compounds kill 50% of the parasites in two hours at a concentration of 100 µg/mL. Importantly, the peptide and alkoxyamine fragments that are unable to generate alkyl radicals display no activity. This strong evidence validates the proposed mechanism: a specific activation of the prodrugs by the parasite proteases leading to parasite death through in situ alkyl radical generation.
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hal-04632259 , version 1 (02-07-2024)

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Ange W Embo-Ibouanga, Michel Nguyen, Jean-Patrick Joly, Mathilde Coustets, Jean-Michel Augereau, et al.. Peptide-Alkoxyamine Drugs: An Innovative Approach to Fight Schistosomiasis: “Digging Their Graves with Their Forks”. Pathogens, 2024, 13 (6), pp.482. ⟨10.3390/pathogens13060482⟩. ⟨hal-04632259⟩

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