2. Academic Validation
  3. Synthesis and biological activity of pyrazole analogues of the staurosporine aglycon K252c

Synthesis and biological activity of pyrazole analogues of the staurosporine aglycon K252c

  • Bioorg Med Chem. 2016 Jul 15;24(14):3116-24. doi: 10.1016/j.bmc.2016.05.032.
Yannick J Esvan 1,  Francis Giraud 1,  Elisabeth Pereira 1,  Virginie Suchaud 1,  Lionel Nauton 1,  Vincent Théry 1,  Lyubov G Dezhenkova 2,  Dmitry N Kaluzhny 3,  Vsevolod N Mazov 4,  Alexander A Shtil 5,  Fabrice Anizon 6,  Pascale Moreau 7
Affiliations

Affiliations

  • 1 Université Clermont Auvergne, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, F-63178 Aubière, France.
  • 2 Gause Institute of New Antibiotics, 119021 Moscow, Russian Federation.
  • 3 Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
  • 4 National University of Science and Technology 'MISIS', 119991 Moscow, Russian Federation.
  • 5 National University of Science and Technology 'MISIS', 119991 Moscow, Russian Federation; Blokhin Cancer Center, 115478 Moscow, Russian Federation.
  • 6 Université Clermont Auvergne, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, F-63178 Aubière, France. Electronic address: [email protected].
  • 7 Université Clermont Auvergne, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, F-63178 Aubière, France. Electronic address: [email protected].
PMID: 27255178 DOI: 10.1016/j.bmc.2016.05.032
Abstract

A derivative of the staurosporine aglycon (K252c), in which the lactam ring was replaced by a pyrazole moiety, was synthesized. The resulting indolopyrazolocarbazole (3) inhibited Pim isoforms 1-3 whereas it did not impair the activity of two known targets of K252c, protein kinase C isoforms α and γ. Compound 3 exhibited moderate cytotoxic activity toward human leukemia and colon carcinoma cell lines (K562 and HCT116), strongly suggesting that this new scaffold deserves further investigations for treatment of malignancies associated with Pim activity.

Keywords

Cytotoxicity; Molecular modeling; Pim kinase inhibition; Pyrazole; Staurosporine aglycon.

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