Pyrazolo[3,4-d]pyrimidines as Potent Antiproliferative and Proapoptotic Agents toward A431 and 8701-BC Cells in Culture via Inhibition of c-Src Phosphorylation

• Published in: Journal of medicinal chemistry Vol. 49; no. 5; pp. 1549 - 1561
• Main Authors: Carraro, Fabio, Naldini, Antonella, Pucci, Annalisa, Locatelli, Giada A, Maga, Giovanni, Schenone, Silvia, Bruno, Olga, Ranise, Angelo, Bondavalli, Francesco, Brullo, Chiara, Fossa, Paola, Menozzi, Giulia, Mosti, Luisa, Modugno, Michele, Tintori, Cristina, Manetti, Fabrizio, Botta, Maurizio
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 09.03.2006; Amer Chemical Soc
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Biological and medical sciences; Cell Line, Tumor; Chemistry, Medicinal; Cyclins - antagonists & inhibitors; Cyclins - biosynthesis; Cyclins - genetics; Drug Screening Assays, Antitumor; General aspects; Humans; Life Sciences & Biomedicine; Medical sciences; Models, Molecular; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Phosphorylation; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - genetics; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; RNA, Messenger - biosynthesis; Science & Technology; src-Family Kinases - metabolism; SIGNAL-TRANSDUCTION; POLY(ADP-RIBOSE) POLYMERASE; ACTIVATION; CANCER METASTASIS; FAMILY KINASES; HUMAN-BREAST; KINASE INHIBITORS; TYROSINE KINASES; DUCTAL INFILTRATING CARCINOMA; HUMAN TUMORS; Antineoplastic agent; Human; Squamous cell carcinoma; Phosphorylation; Gene product; Malignant tumor; Organic chlorine compounds; In vitro; Modeling; Cell line; Structure activity relation; C-Onc gene; Molecular model; Mammary gland; Inhibition; Mechanism of action; Chemical synthesis; Tumor cell; Apoptosis

We report here the synthesis of new pyrazolo[3,4-d]pyrimidine derivatives along with their biological properties as inhibitors of isolated Src and cell line proliferation (A431 and 8701-BC cells). Such compounds block the growth of cancer cells by interfering with the phosphorylation of Src, and the...