title: Antiproliferative activity of new 1-aryl-4-amino-1H-pyrazolo[3,4-d]pyrimidine derivatives toward the human epidermoid carcinoma A431 cell line.
abstract: Synthesis and biological evaluation of a new class of 1-aryl-4-amino-1H-pyrazolo[3,4-d]pyrimidine derivatives are reported. A preliminary cellular assay system using the tumor cell line A431 responding to epidermal growth factor (EGF) for its growth, shows that the new compounds are potent inhibitors of cell growth. The inhibition of tumor cell proliferation is not associated with blockage of EGF receptor (EGFR), but substantially due to the interference with the signalling pathway at the level of Src tyrosine kinase and at the level of the downstream effector signal mitogen activated protein kinases (MAPKs), ERK1-2.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV, 16132 Genova, Italy. schensil@unige.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Schenone
authors.forename: Olga
authors.initials: O
authors.lastname: Bruno
authors.forename: Francesco
authors.initials: F
authors.lastname: Bondavalli
authors.forename: Angelo
authors.initials: A
authors.lastname: Ranise
authors.forename: Luisa
authors.initials: L
authors.lastname: Mosti
authors.forename: Giulia
authors.initials: G
authors.lastname: Menozzi
authors.forename: Paola
authors.initials: P
authors.lastname: Fossa
authors.forename: Sandra
authors.initials: S
authors.lastname: Donnini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Santoro
authors.forename: Marina
authors.initials: M
authors.lastname: Ziche
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manetti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D011743:Pyrimidines; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases