title: Synthesis, biological evaluation and docking studies of 4-amino substituted 1H-pyrazolo[3,4-d]pyrimidines.
abstract: The synthesis of new 4-amino substituted pyrazolo[3,4-d]pyrimidines along with their activity in cell-free enzymatic assays on Src and Abl tyrosine kinases is reported. Some compounds emerged as good dual inhibitors of the two enzymes, showed antiproliferative effects on two Bcr-Abl positive leukemia cell lines K-562 and KU-812, and induced apoptosis, as demonstrated by the PARP assay. Docking studies have been also performed to analyze the binding mode of compounds under study and to identify the structural determinants of their interaction with both Src and Abl.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV 3, I-16132 Genova, Italy. schensil@unige.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Schenone
authors.forename: Chiara
authors.initials: C
authors.lastname: Brullo
authors.forename: Olga
authors.initials: O
authors.lastname: Bruno
authors.forename: Francesco
authors.initials: F
authors.lastname: Bondavalli
authors.forename: Luisa
authors.initials: L
authors.lastname: Mosti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.forename: Emmanuele
authors.initials: E
authors.lastname: Crespan
authors.forename: Fabio
authors.initials: F
authors.lastname: Carraro
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manetti
authors.forename: Cristina
authors.initials: C
authors.lastname: Tintori
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000081247:CSK Tyrosine-Protein Kinase; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D016044:Fusion Proteins, bcr-abl; D019061:src-Family Kinases; C000631346:CSK protein, human