Antiproliferative activity of new 1-aryl-4-amino-1H-pyrazolo[3,4-d]pyrimidine derivatives toward the human epidermoid carcinoma A431 cell line.
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.
Schenone
Silvia
S
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV, 16132 Genova, Italy. schensil@unige.it
Bruno
Olga
O
Bondavalli
Francesco
F
Ranise
Angelo
A
Mosti
Luisa
L
Menozzi
Giulia
G
Fossa
Paola
P
Donnini
Sandra
S
Santoro
Annalisa
A
Ziche
Marina
M
Manetti
Fabrizio
F
Botta
Maurizio
M
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
D000970:Antineoplastic Agents; D011720:Pyrazoles; D011743:Pyrimidines; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases