title: Synthesis and biological activity of pyrazole analogues of the staurosporine aglycon K252c.
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.
authors.affiliation: 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.
authors.forename: Yannick J
authors.initials: YJ
authors.lastname: Esvan
authors.affiliation: 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.
authors.forename: Francis
authors.initials: F
authors.lastname: Giraud
authors.affiliation: 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.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pereira
authors.affiliation: 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.
authors.forename: Virginie
authors.initials: V
authors.lastname: Suchaud
authors.affiliation: 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.
authors.forename: Lionel
authors.initials: L
authors.lastname: Nauton
authors.affiliation: 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.
authors.forename: Vincent
authors.initials: V
authors.lastname: Théry
authors.affiliation: Gause Institute of New Antibiotics, 119021 Moscow, Russian Federation.
authors.forename: Lyubov G
authors.initials: LG
authors.lastname: Dezhenkova
authors.affiliation: Engelhardt Institute of Molecular Biology, 119991 Moscow, Russian Federation.
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Kaluzhny
authors.affiliation: National University of Science and Technology 'MISIS', 119991 Moscow, Russian Federation.
authors.forename: Vsevolod N
authors.initials: VN
authors.lastname: Mazov
authors.affiliation: National University of Science and Technology 'MISIS', 119991 Moscow, Russian Federation; Blokhin Cancer Center, 115478 Moscow, Russian Federation.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shtil
authors.affiliation: 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: Fabrice.ANIZON@univ-bpclermont.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Anizon
authors.affiliation: 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: Pascale.MOREAU@univ-bpclermont.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Moreau
mesh_terms: D066241:Carbon-13 Magnetic Resonance Spectroscopy; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D020014:K562 Cells; D008958:Models, Molecular; D011493:Protein Kinase C / Q000187:drug effects; D051571:Protein Kinase C-alpha / Q000187:drug effects; D066244:Proton Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D019311:Staurosporine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011720:Pyrazoles; C087857:protein kinase C gamma; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D019311:Staurosporine
keywords: Cytotoxicity; Molecular modeling; Pim kinase inhibition; Pyrazole; Staurosporine aglycon