title: Identification of a novel pyrazolo[3,4-d]pyrimidine able to inhibit cell proliferation of a human osteogenic sarcoma in vitro and in a xenograft model in mice.
abstract: New pyrazolo[3,4-d]pyrimidines were synthesized and found to inhibit Src phosphorylation in a cell-free assay. Some of them significantly reduced the growth of human osteogenic sarcoma (SaOS-2) cells. The best compound, in terms of inhibitory properties toward both Src and SaOS-2 cells, was further investigated and found to reduce bone resorption when used to treat mouse osteoclasts, without interfering with normal osteoblast growth. Moreover, its metabolic stability prompted its study on a human SaOS-2 xenograft tumor model in nude mice, where the compound reduced significantly both the volume and weight of the tumor. These experimental findings make the new compound an interesting hit in the field of bone-related diseases.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Siena, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manetti
authors.forename: Annalisa
authors.initials: A
authors.lastname: Santucci
authors.forename: Giada A
authors.initials: GA
authors.lastname: Locatelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.forename: Adriano
authors.initials: A
authors.lastname: Spreafico
authors.forename: Tommaso
authors.initials: T
authors.lastname: Serchi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Orlandini
authors.forename: Giulia
authors.initials: G
authors.lastname: Bernardini
authors.forename: Nicola P
authors.initials: NP
authors.lastname: Caradonna
authors.forename: Andrea
authors.initials: A
authors.lastname: Spallarossa
authors.forename: Chiara
authors.initials: C
authors.lastname: Brullo
authors.forename: Silvia
authors.initials: S
authors.lastname: Schenone
authors.forename: Olga
authors.initials: O
authors.lastname: Bruno
authors.forename: Angelo
authors.initials: A
authors.lastname: Ranise
authors.forename: Francesco
authors.initials: F
authors.lastname: Bondavalli
authors.forename: Oskar
authors.initials: O
authors.lastname: Hoffmann
authors.forename: Mauro
authors.initials: M
authors.lastname: Bologna
authors.forename: Adriano
authors.initials: A
authors.lastname: Angelucci
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001862:Bone Resorption / Q000517:prevention & control; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; D019061:src-Family Kinases