2. Academic Validation
  3. 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

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

  • J Med Chem. 2006 Mar 9;49(5):1549-61. doi: 10.1021/jm050603r.
Fabio Carraro 1,  Antonella Naldini,  Annalisa Pucci,  Giada A Locatelli,  Giovanni Maga,  Silvia Schenone,  Olga Bruno,  Angelo Ranise,  Francesco Bondavalli,  Chiara Brullo,  Paola Fossa,  Giulia Menozzi,  Luisa Mosti,  Michele Modugno,  Cristina Tintori,  Fabrizio Manetti,  Maurizio Botta
Affiliations

Affiliation

  • 1 Dipartimento di Fisiologia, Sezione di Neuroimmunofisiologia, Università degli Studi di Siena, Via Aldo Moro, I-53100, Siena, Italy.
PMID: 16509573 DOI: 10.1021/jm050603r
Abstract

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 they act as proapoptotic agents through the inhibition of the anti apoptotic gene BCL2. Several of them were found to be more active than the reference compound (1-(tert-butyl)-3-(4-chlorophenyl)-4-aminopyrazolo[3,4-d]pyrimidine, PP2) in inhibiting cell proliferation and in inducing Apoptosis, and as active as PP2 in the inhibition of the phosphorylation of isolated Src. Moreover, molecular modeling simulations have been performed to hypothesize the way, at the molecular level, by which the inhibitors were able to act as antiproliferative agents.

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