Marine-Derived 2-Aminoimidazolone Alkaloids. Leucettamine B-Related Polyandrocarpamines Inhibit Mammalian and Protozoan DYRK & CLK Kinases

Abstract : A large diversity of 2-aminoimidazolone alkaloids is produced by various marine invertebrates, especially by the marine Calcareous sponges Leucetta and Clathrina. The phylogeny of these sponges and the wide scope of 2-aminoimidazolone alkaloids they produce are reviewed in this article. The origin (invertebrate cells, associated microorganisms, or filtered plankton), physiological functions, and natural molecular targets of these alkaloids are largely unknown. Following the identification of leucettamine B as an inhibitor of selected protein kinases, we synthesized a family of analogues, collectively named leucettines, as potent inhibitors of DYRKs (dual-specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases) and potential pharmacological leads for the treatment of several diseases, including Alzheimer's disease and Down syndrome. We assembled a small library of marine sponge- and ascidian-derived 2-aminoimidazolone alkaloids, along with several synthetic analogues, and tested them on a panel of mammalian and protozoan kinases. Polyandrocarpamines A and B were found to be potent and selective inhibitors of DYRKs and CLKs. They inhibited cyclin D1 phosphorylation on a DYRK1A phosphosite in cultured cells. 2-Aminoimidazolones thus represent a promising chemical scaffold for the design of potential therapeutic drug candidates acting as specific inhibitors of disease-relevant kinases, and possibly other disease-relevant targets.
Type de document :
Article dans une revue
Marine drugs, MDPI, 2017, 15 (10), pp.316 -. 〈10.3390/md15100316〉
Domaine :
Liste complète des métadonnées

Littérature citée [7 références]  Voir  Masquer  Télécharger

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01640115
Contributeur : Laurent Jonchère <>
Soumis le : mercredi 27 juin 2018 - 10:21:25
Dernière modification le : vendredi 31 août 2018 - 09:18:06

Fichier

Loaec - Marine-Derived 2-Amino...
Fichiers éditeurs autorisés sur une archive ouverte

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Citation

Nadège Loaëc, Eletta Attanasio, Benoît Villiers, Emilie Durieu, Tania Tahtouh, et al.. Marine-Derived 2-Aminoimidazolone Alkaloids. Leucettamine B-Related Polyandrocarpamines Inhibit Mammalian and Protozoan DYRK & CLK Kinases. Marine drugs, MDPI, 2017, 15 (10), pp.316 -. 〈10.3390/md15100316〉. 〈hal-01640115〉

Partager

Métriques

Consultations de la notice

118

Téléchargements de fichiers

14