{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:29:23Z","timestamp":1792542563920,"version":"4.5.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T00:00:00Z","timestamp":1508198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/md15100316","type":"journal-article","created":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T11:14:35Z","timestamp":1508238875000},"page":"316","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Marine-Derived 2-Aminoimidazolone Alkaloids. Leucettamine B-Related Polyandrocarpamines Inhibit Mammalian and Protozoan DYRK &amp; CLK Kinases"],"prefix":"10.3390","volume":"15","author":[{"given":"Nad\u00e8ge","family":"Loa\u00ebc","sequence":"first","affiliation":[{"name":"ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France"},{"name":"Station Biologique de Roscoff, CNRS, \u2018Protein Phosphorylation and Human Disease\u2019 Group, Place G. Teissier, 29680 Roscoff, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eletta","family":"Attanasio","sequence":"additional","affiliation":[{"name":"ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno\u00eet","family":"Villiers","sequence":"additional","affiliation":[{"name":"ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Durieu","sequence":"additional","affiliation":[{"name":"ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Tahtouh","sequence":"additional","affiliation":[{"name":"ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Cam","sequence":"additional","affiliation":[{"name":"ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4291-7573","authenticated-orcid":false,"given":"Rohan","family":"Davis","sequence":"additional","affiliation":[{"name":"Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Alencar","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro, Instituto de Biologia\u2014Departamento de Zoologia, Av. Carlos Chagas Filho 373-CCS-Bloco A-Sala A0-100, Ilha do Fund\u00e3o, 21941-902 Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Rou\u00e9","sequence":"additional","affiliation":[{"name":"Mol\u00e9cules de Communication et Adaptation des Micro-Organismes, UMR 7245 CNRS, Mus\u00e9um National d\u2019 Histoire Naturelle, 57 rue Cuvier (C.P. 54), 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Lise","family":"Bourguet-Kondracki","sequence":"additional","affiliation":[{"name":"Mol\u00e9cules de Communication et Adaptation des Micro-Organismes, UMR 7245 CNRS, Mus\u00e9um National d\u2019 Histoire Naturelle, 57 rue Cuvier (C.P. 54), 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Proksch","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pharmazeutische Biologie und Biotechnologie, Universit\u00e4tsstr. 1, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Limanton","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), B\u00e2t. 10A, Campus de Beaulieu, Avenue du G\u00e9n\u00e9ral Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol\u00e8ne","family":"Guiheneuf","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), B\u00e2t. 10A, Campus de Beaulieu, Avenue du G\u00e9n\u00e9ral Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Carreaux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), B\u00e2t. 10A, Campus de Beaulieu, Avenue du G\u00e9n\u00e9ral Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Bazureau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), B\u00e2t. 10A, Campus de Beaulieu, Avenue du G\u00e9n\u00e9ral Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Klautau","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro, Instituto de Biologia\u2014Departamento de Zoologia, Av. 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