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Synthesis and biological evaluation of 1H-pyrrolo[3,2-g]isoquinolines.
Defois, Mathilde; Josselin, Béatrice; Brindeau, Pierre; Krämer, Andreas; Knapp, Stefan; Anizon, Fabrice; Giraud, Francis; Ruchaud, Sandrine; Moreau, Pascale.
  • Defois M; Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, F-63000 Clermont-Ferrand, France.
  • Josselin B; Sorbonne Université, CNRS, UMR8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680 Roscoff, France; Sorbonne Université, CNRS, FR2424, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening facility), Station Biologique de Roscoff, 29680 R
  • Brindeau P; Sorbonne Université, CNRS, UMR8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680 Roscoff, France.
  • Krämer A; Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany; Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany.
  • Knapp S; Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany; Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany.
  • Anizon F; Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, F-63000 Clermont-Ferrand, France.
  • Giraud F; Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, F-63000 Clermont-Ferrand, France. Electronic address: francis.giraud@uca.fr.
  • Ruchaud S; Sorbonne Université, CNRS, UMR8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680 Roscoff, France. Electronic address: sruchaud@sb-roscoff.fr.
  • Moreau P; Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, F-63000 Clermont-Ferrand, France. Electronic address: pascale.moreau@uca.fr.
Bioorg Med Chem ; 100: 117619, 2024 Feb 15.
Article en En | MEDLINE | ID: mdl-38320389
ABSTRACT
A structure-activity relationship study performed on 1H-pyrrolo[3,2-g]isoquinoline scaffold identified new haspin inhibitors with nanomolar potencies and selectivity indices (SI) over 6 (inhibitory potency evaluated against 8 protein kinases). Compound 22 was the most active of the series (haspin IC50 = 76 nM). Cellular evaluation of 22 confirmed its activity for endogenous haspin in U-2 OS cells and its anti-proliferative activity against various cell lines. In addition, the binding mode of analog 22 in complex with haspin was determined by X-ray crystallography.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pirroles / Proteínas Serina-Treonina Quinasas / Inhibidores de Proteínas Quinasas Idioma: En Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pirroles / Proteínas Serina-Treonina Quinasas / Inhibidores de Proteínas Quinasas Idioma: En Año: 2024 Tipo del documento: Article