AustralieFrV1, Main, Exploration, bibRecord, 000829

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

Identifieur interne : 000829 ( Main/Exploration ); précédent : 000828; suivant : 000830

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

Auteurs : Nadège Loaëc [France] ; Eletta Attanasio ; Benoît Villiers ; Emilie Durieu ; Tania Tahtouh ; Morgane Cam ; Rohan A. Davis ; Aline Alencar ; Mélanie Roué ; Marie-Lise Bourguet-Kondracki ; Peter Proksch ; Emmanuelle Limanton ; Solène Guiheneuf ; François Carreaux ; Jean-Pierre Bazureau ; Michelle Klautau ; Laurent Meijer

Source :

Marine Drugs [ 1660-3397 ] ; 2017.

RBID : PMC:5666424

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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666424

DOI: 10.3390/md15100316
PubMed: 29039762
PubMed Central: 5666424

Affiliations:

France

Le document en format XML

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<author><name sortKey="Loaec, Nadege" sort="Loaec, Nadege" uniqKey="Loaec N" first="Nadège" last="Loaëc">Nadège Loaëc</name>
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 (E.A.);<email>bvilliers@yahoo.fr</email>
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<author><name sortKey="Attanasio, Eletta" sort="Attanasio, Eletta" uniqKey="Attanasio E" first="Eletta" last="Attanasio">Eletta Attanasio</name>
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<author><name sortKey="Villiers, Benoit" sort="Villiers, Benoit" uniqKey="Villiers B" first="Benoît" last="Villiers">Benoît Villiers</name>
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<author><name sortKey="Durieu, Emilie" sort="Durieu, Emilie" uniqKey="Durieu E" first="Emilie" last="Durieu">Emilie Durieu</name>
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<author><name sortKey="Tahtouh, Tania" sort="Tahtouh, Tania" uniqKey="Tahtouh T" first="Tania" last="Tahtouh">Tania Tahtouh</name>
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 (N.L.);<email>attanasio@manros-therapeutics.com</email>
 (E.A.);<email>bvilliers@yahoo.fr</email>
 (B.V.);<email>durieu@manros-therapeutics.com</email>
 (E.D.);<email>tania.tahtouh@gmail.com</email>
 (T.T.);<email>cam.morgane@live.fr</email>
 (M.C.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cam, Morgane" sort="Cam, Morgane" uniqKey="Cam M" first="Morgane" last="Cam">Morgane Cam</name>
<affiliation><nlm:aff id="af1-marinedrugs-15-00316">ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France;<email>nadege.loaec@univ-brest.fr</email>
 (N.L.);<email>attanasio@manros-therapeutics.com</email>
 (E.A.);<email>bvilliers@yahoo.fr</email>
 (B.V.);<email>durieu@manros-therapeutics.com</email>
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 (M.C.)</nlm:aff>
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<author><name sortKey="Davis, Rohan A" sort="Davis, Rohan A" uniqKey="Davis R" first="Rohan A." last="Davis">Rohan A. Davis</name>
<affiliation><nlm:aff id="af3-marinedrugs-15-00316">Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia;<email>r.davis@griffith.edu.au</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Alencar, Aline" sort="Alencar, Aline" uniqKey="Alencar A" first="Aline" last="Alencar">Aline Alencar</name>
<affiliation><nlm:aff id="af4-marinedrugs-15-00316">Universidade Federal do Rio de Janeiro, Instituto de Biologia—Departamento de Zoologia, Av. Carlos Chagas Filho 373-CCS-Bloco A-Sala A0-100, Ilha do Fundão, 21941-902 Rio de Janeiro, Brazil;<email>aalencar@biologia.ufrj.br</email>
</nlm:aff>
</affiliation>
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<author><name sortKey="Roue, Melanie" sort="Roue, Melanie" uniqKey="Roue M" first="Mélanie" last="Roué">Mélanie Roué</name>
<affiliation><nlm:aff id="af5-marinedrugs-15-00316">Molécules de Communication et Adaptation des Micro-Organismes, UMR 7245 CNRS, Muséum National d’ Histoire Naturelle, 57 rue Cuvier (C.P. 54), 75005 Paris, France;<email>mroue@mnhn.fr</email>
 (M.R.);<email>bourguet@mnhn.fr</email>
 (M.-L.B.-K.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bourguet Kondracki, Marie Lise" sort="Bourguet Kondracki, Marie Lise" uniqKey="Bourguet Kondracki M" first="Marie-Lise" last="Bourguet-Kondracki">Marie-Lise Bourguet-Kondracki</name>
<affiliation><nlm:aff id="af5-marinedrugs-15-00316">Molécules de Communication et Adaptation des Micro-Organismes, UMR 7245 CNRS, Muséum National d’ Histoire Naturelle, 57 rue Cuvier (C.P. 54), 75005 Paris, France;<email>mroue@mnhn.fr</email>
 (M.R.);<email>bourguet@mnhn.fr</email>
 (M.-L.B.-K.)</nlm:aff>
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<author><name sortKey="Proksch, Peter" sort="Proksch, Peter" uniqKey="Proksch P" first="Peter" last="Proksch">Peter Proksch</name>
<affiliation><nlm:aff id="af6-marinedrugs-15-00316">Institut für Pharmazeutische Biologie und Biotechnologie, Universitätsstr. 1, 40225 Düsseldorf, Germany;<email>proksch@duesseldorf-uni.de</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Limanton, Emmanuelle" sort="Limanton, Emmanuelle" uniqKey="Limanton E" first="Emmanuelle" last="Limanton">Emmanuelle Limanton</name>
<affiliation><nlm:aff id="af7-marinedrugs-15-00316">Université de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France;<email>emmanuelle.limanton@univ-rennes1.fr</email>
 (E.L.);<email>solene.guiheneuf@univ-rennes1.fr</email>
 (S.G.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Guiheneuf, Solene" sort="Guiheneuf, Solene" uniqKey="Guiheneuf S" first="Solène" last="Guiheneuf">Solène Guiheneuf</name>
<affiliation><nlm:aff id="af7-marinedrugs-15-00316">Université de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France;<email>emmanuelle.limanton@univ-rennes1.fr</email>
 (E.L.);<email>solene.guiheneuf@univ-rennes1.fr</email>
 (S.G.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Carreaux, Francois" sort="Carreaux, Francois" uniqKey="Carreaux F" first="François" last="Carreaux">François Carreaux</name>
<affiliation><nlm:aff id="af7-marinedrugs-15-00316">Université de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France;<email>emmanuelle.limanton@univ-rennes1.fr</email>
 (E.L.);<email>solene.guiheneuf@univ-rennes1.fr</email>
 (S.G.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bazureau, Jean Pierre" sort="Bazureau, Jean Pierre" uniqKey="Bazureau J" first="Jean-Pierre" last="Bazureau">Jean-Pierre Bazureau</name>
<affiliation><nlm:aff id="af7-marinedrugs-15-00316">Université de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France;<email>emmanuelle.limanton@univ-rennes1.fr</email>
 (E.L.);<email>solene.guiheneuf@univ-rennes1.fr</email>
 (S.G.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Klautau, Michelle" sort="Klautau, Michelle" uniqKey="Klautau M" first="Michelle" last="Klautau">Michelle Klautau</name>
<affiliation><nlm:aff id="af4-marinedrugs-15-00316">Universidade Federal do Rio de Janeiro, Instituto de Biologia—Departamento de Zoologia, Av. Carlos Chagas Filho 373-CCS-Bloco A-Sala A0-100, Ilha do Fundão, 21941-902 Rio de Janeiro, Brazil;<email>aalencar@biologia.ufrj.br</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Meijer, Laurent" sort="Meijer, Laurent" uniqKey="Meijer L" first="Laurent" last="Meijer">Laurent Meijer</name>
<affiliation><nlm:aff id="af1-marinedrugs-15-00316">ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France;<email>nadege.loaec@univ-brest.fr</email>
 (N.L.);<email>attanasio@manros-therapeutics.com</email>
 (E.A.);<email>bvilliers@yahoo.fr</email>
 (B.V.);<email>durieu@manros-therapeutics.com</email>
 (E.D.);<email>tania.tahtouh@gmail.com</email>
 (T.T.);<email>cam.morgane@live.fr</email>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Marine-Derived 2-Aminoimidazolone Alkaloids. Leucettamine B-Related Polyandrocarpamines Inhibit Mammalian and Protozoan DYRK & CLK Kinases</title>
<author><name sortKey="Loaec, Nadege" sort="Loaec, Nadege" uniqKey="Loaec N" first="Nadège" last="Loaëc">Nadège Loaëc</name>
<affiliation><nlm:aff id="af1-marinedrugs-15-00316">ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France;<email>nadege.loaec@univ-brest.fr</email>
 (N.L.);<email>attanasio@manros-therapeutics.com</email>
 (E.A.);<email>bvilliers@yahoo.fr</email>
 (B.V.);<email>durieu@manros-therapeutics.com</email>
 (E.D.);<email>tania.tahtouh@gmail.com</email>
 (T.T.);<email>cam.morgane@live.fr</email>
 (M.C.)</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2-marinedrugs-15-00316">Station Biologique de Roscoff, CNRS, ‘Protein Phosphorylation and Human Disease’ Group, Place G. Teissier, 29680 Roscoff, Bretagne, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Station Biologique de Roscoff, CNRS, ‘Protein Phosphorylation and Human Disease’ Group, Place G. Teissier, 29680 Roscoff, Bretagne</wicri:regionArea>
<wicri:noRegion>Bretagne</wicri:noRegion>
<wicri:noRegion>Bretagne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Attanasio, Eletta" sort="Attanasio, Eletta" uniqKey="Attanasio E" first="Eletta" last="Attanasio">Eletta Attanasio</name>
<affiliation><nlm:aff id="af1-marinedrugs-15-00316">ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France;<email>nadege.loaec@univ-brest.fr</email>
 (N.L.);<email>attanasio@manros-therapeutics.com</email>
 (E.A.);<email>bvilliers@yahoo.fr</email>
 (B.V.);<email>durieu@manros-therapeutics.com</email>
 (E.D.);<email>tania.tahtouh@gmail.com</email>
 (T.T.);<email>cam.morgane@live.fr</email>
 (M.C.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Villiers, Benoit" sort="Villiers, Benoit" uniqKey="Villiers B" first="Benoît" last="Villiers">Benoît Villiers</name>
<affiliation><nlm:aff id="af1-marinedrugs-15-00316">ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France;<email>nadege.loaec@univ-brest.fr</email>
 (N.L.);<email>attanasio@manros-therapeutics.com</email>
 (E.A.);<email>bvilliers@yahoo.fr</email>
 (B.V.);<email>durieu@manros-therapeutics.com</email>
 (E.D.);<email>tania.tahtouh@gmail.com</email>
 (T.T.);<email>cam.morgane@live.fr</email>
 (M.C.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Durieu, Emilie" sort="Durieu, Emilie" uniqKey="Durieu E" first="Emilie" last="Durieu">Emilie Durieu</name>
<affiliation><nlm:aff id="af1-marinedrugs-15-00316">ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France;<email>nadege.loaec@univ-brest.fr</email>
 (N.L.);<email>attanasio@manros-therapeutics.com</email>
 (E.A.);<email>bvilliers@yahoo.fr</email>
 (B.V.);<email>durieu@manros-therapeutics.com</email>
 (E.D.);<email>tania.tahtouh@gmail.com</email>
 (T.T.);<email>cam.morgane@live.fr</email>
 (M.C.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tahtouh, Tania" sort="Tahtouh, Tania" uniqKey="Tahtouh T" first="Tania" last="Tahtouh">Tania Tahtouh</name>
<affiliation><nlm:aff id="af1-marinedrugs-15-00316">ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France;<email>nadege.loaec@univ-brest.fr</email>
 (N.L.);<email>attanasio@manros-therapeutics.com</email>
 (E.A.);<email>bvilliers@yahoo.fr</email>
 (B.V.);<email>durieu@manros-therapeutics.com</email>
 (E.D.);<email>tania.tahtouh@gmail.com</email>
 (T.T.);<email>cam.morgane@live.fr</email>
 (M.C.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cam, Morgane" sort="Cam, Morgane" uniqKey="Cam M" first="Morgane" last="Cam">Morgane Cam</name>
<affiliation><nlm:aff id="af1-marinedrugs-15-00316">ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France;<email>nadege.loaec@univ-brest.fr</email>
 (N.L.);<email>attanasio@manros-therapeutics.com</email>
 (E.A.);<email>bvilliers@yahoo.fr</email>
 (B.V.);<email>durieu@manros-therapeutics.com</email>
 (E.D.);<email>tania.tahtouh@gmail.com</email>
 (T.T.);<email>cam.morgane@live.fr</email>
 (M.C.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Davis, Rohan A" sort="Davis, Rohan A" uniqKey="Davis R" first="Rohan A." last="Davis">Rohan A. Davis</name>
<affiliation><nlm:aff id="af3-marinedrugs-15-00316">Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia;<email>r.davis@griffith.edu.au</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Alencar, Aline" sort="Alencar, Aline" uniqKey="Alencar A" first="Aline" last="Alencar">Aline Alencar</name>
<affiliation><nlm:aff id="af4-marinedrugs-15-00316">Universidade Federal do Rio de Janeiro, Instituto de Biologia—Departamento de Zoologia, Av. Carlos Chagas Filho 373-CCS-Bloco A-Sala A0-100, Ilha do Fundão, 21941-902 Rio de Janeiro, Brazil;<email>aalencar@biologia.ufrj.br</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Roue, Melanie" sort="Roue, Melanie" uniqKey="Roue M" first="Mélanie" last="Roué">Mélanie Roué</name>
<affiliation><nlm:aff id="af5-marinedrugs-15-00316">Molécules de Communication et Adaptation des Micro-Organismes, UMR 7245 CNRS, Muséum National d’ Histoire Naturelle, 57 rue Cuvier (C.P. 54), 75005 Paris, France;<email>mroue@mnhn.fr</email>
 (M.R.);<email>bourguet@mnhn.fr</email>
 (M.-L.B.-K.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bourguet Kondracki, Marie Lise" sort="Bourguet Kondracki, Marie Lise" uniqKey="Bourguet Kondracki M" first="Marie-Lise" last="Bourguet-Kondracki">Marie-Lise Bourguet-Kondracki</name>
<affiliation><nlm:aff id="af5-marinedrugs-15-00316">Molécules de Communication et Adaptation des Micro-Organismes, UMR 7245 CNRS, Muséum National d’ Histoire Naturelle, 57 rue Cuvier (C.P. 54), 75005 Paris, France;<email>mroue@mnhn.fr</email>
 (M.R.);<email>bourguet@mnhn.fr</email>
 (M.-L.B.-K.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Proksch, Peter" sort="Proksch, Peter" uniqKey="Proksch P" first="Peter" last="Proksch">Peter Proksch</name>
<affiliation><nlm:aff id="af6-marinedrugs-15-00316">Institut für Pharmazeutische Biologie und Biotechnologie, Universitätsstr. 1, 40225 Düsseldorf, Germany;<email>proksch@duesseldorf-uni.de</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Limanton, Emmanuelle" sort="Limanton, Emmanuelle" uniqKey="Limanton E" first="Emmanuelle" last="Limanton">Emmanuelle Limanton</name>
<affiliation><nlm:aff id="af7-marinedrugs-15-00316">Université de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France;<email>emmanuelle.limanton@univ-rennes1.fr</email>
 (E.L.);<email>solene.guiheneuf@univ-rennes1.fr</email>
 (S.G.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Guiheneuf, Solene" sort="Guiheneuf, Solene" uniqKey="Guiheneuf S" first="Solène" last="Guiheneuf">Solène Guiheneuf</name>
<affiliation><nlm:aff id="af7-marinedrugs-15-00316">Université de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France;<email>emmanuelle.limanton@univ-rennes1.fr</email>
 (E.L.);<email>solene.guiheneuf@univ-rennes1.fr</email>
 (S.G.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Carreaux, Francois" sort="Carreaux, Francois" uniqKey="Carreaux F" first="François" last="Carreaux">François Carreaux</name>
<affiliation><nlm:aff id="af7-marinedrugs-15-00316">Université de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France;<email>emmanuelle.limanton@univ-rennes1.fr</email>
 (E.L.);<email>solene.guiheneuf@univ-rennes1.fr</email>
 (S.G.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bazureau, Jean Pierre" sort="Bazureau, Jean Pierre" uniqKey="Bazureau J" first="Jean-Pierre" last="Bazureau">Jean-Pierre Bazureau</name>
<affiliation><nlm:aff id="af7-marinedrugs-15-00316">Université de Rennes 1, Institut des Sciences Chimiques de Rennes, ISCR UMR CNRS 6226, Groupe Chimie Organique et Interfaces (CORINT), Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes CEDEX, Bretagne, France;<email>emmanuelle.limanton@univ-rennes1.fr</email>
 (E.L.);<email>solene.guiheneuf@univ-rennes1.fr</email>
 (S.G.)</nlm:aff>
</affiliation>
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<author><name sortKey="Klautau, Michelle" sort="Klautau, Michelle" uniqKey="Klautau M" first="Michelle" last="Klautau">Michelle Klautau</name>
<affiliation><nlm:aff id="af4-marinedrugs-15-00316">Universidade Federal do Rio de Janeiro, Instituto de Biologia—Departamento de Zoologia, Av. Carlos Chagas Filho 373-CCS-Bloco A-Sala A0-100, Ilha do Fundão, 21941-902 Rio de Janeiro, Brazil;<email>aalencar@biologia.ufrj.br</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Meijer, Laurent" sort="Meijer, Laurent" uniqKey="Meijer L" first="Laurent" last="Meijer">Laurent Meijer</name>
<affiliation><nlm:aff id="af1-marinedrugs-15-00316">ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, Bretagne, France;<email>nadege.loaec@univ-brest.fr</email>
 (N.L.);<email>attanasio@manros-therapeutics.com</email>
 (E.A.);<email>bvilliers@yahoo.fr</email>
 (B.V.);<email>durieu@manros-therapeutics.com</email>
 (E.D.);<email>tania.tahtouh@gmail.com</email>
 (T.T.);<email>cam.morgane@live.fr</email>
 (M.C.)</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Marine Drugs</title>
<idno type="eISSN">1660-3397</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>A large diversity of 2-aminoimidazolone alkaloids is produced by various marine invertebrates, especially by the marine Calcareous sponges <italic>Leucetta</italic>
 and <italic>Clathrina</italic>
. 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.</p>
</div>
</front>
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Serveur d'exploration sur les relations entre la France et l'Australie

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

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

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	Serveur d'exploration sur les relations entre la France et l'Australie
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