@article{fdi:010073596,
  title = {{M}arine-derived 2-aminoimidazolone alkaloids. {L}eucettamine {B}-related polyandrocarpamines inhibit mammalian and protozoan {DYRK} & {CLK} kinases},
  author = {{L}oaec, {N}. and {A}ttanasio, {E}. and {V}illiers, {B}. and {D}urieu, {E}. and {T}ahtouh, {T}. and {C}am, {M}. and {D}avis, {R}. {A}. and {A}lencar, {A}. and {R}ou{\'e}, {M}{\'e}lanie and {B}ourguet-{K}ondracki, {M}. {L}. and {P}roksch, {P}. and {L}imanton, {E}. and {G}uiheneuf, {S}. and {C}arreaux, {F}. and {B}azureau, {J}. {P}. and {K}lautau, {M}. and {M}eijer, {L}.},
  editor = {},
  language = {{ENG}},
  abstract = {{A} large diversity of 2-aminoimidazolone alkaloids is produced by various marine invertebrates, especially by the marine {C}alcareous sponges {L}eucetta and {C}lathrina. {T}he phylogeny of these sponges and the wide scope of 2-aminoimidazolone alkaloids they produce are reviewed in this article. {T}he origin (invertebrate cells, associated microorganisms, or filtered plankton), physiological functions, and natural molecular targets of these alkaloids are largely unknown. {F}ollowing 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 {DYRK}s (dual-specificity, tyrosine phosphorylation regulated kinases) and {CLK}s (cdc2-like kinases) and potential pharmacological leads for the treatment of several diseases, including {A}lzheimer's disease and {D}own syndrome. {W}e 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. {P}olyandrocarpamines {A} and {B} were found to be potent and selective inhibitors of {DYRK}s and {CLK}s. {T}hey inhibited cyclin {D}1 phosphorylation on a {DYRK}1{A} phosphosite in cultured cells. 2-{A}minoimidazolones 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.},
  keywords = {marine sponge ; {P}orifera ; {C}alcarea ; ascidian ; {P}olyandrocarpa ; 2-aminoimidazolone alkaloids ; leucettamine {B} ; leucettine ; polyandrocarpamines ; protein kinases ; {DYRK} ; {CLK} ; kinase inhibitor ; {A}lzheimer's disease ; {D}own syndrome},
  booktitle = {},
  journal = {{M}arine {D}rugs},
  volume = {15},
  numero = {10},
  pages = {art. 316 [15 p.]},
  ISSN = {1660-3397},
  year = {2017},
  DOI = {10.3390/md15100316},
  URL = {https://www.documentation.ird.fr/hor/fdi:010073596},
}