Schenone Silvia, Brullo Chiara, Bruno Olga, Bondavalli Francesco, Mosti Luisa, Maga Giovanni, Crespan Emmanuele, Carraro Fabio, Manetti Fabrizio, Tintori Cristina, Botta Maurizio
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV 3, I-16132 Genova, Italy.
Eur J Med Chem. 2008 Dec;43(12):2665-76. doi: 10.1016/j.ejmech.2008.01.034. Epub 2008 Feb 6.
The synthesis of new 4-amino substituted pyrazolo[3,4-d]pyrimidines along with their activity in cell-free enzymatic assays on Src and Abl tyrosine kinases is reported. Some compounds emerged as good dual inhibitors of the two enzymes, showed antiproliferative effects on two Bcr-Abl positive leukemia cell lines K-562 and KU-812, and induced apoptosis, as demonstrated by the PARP assay. Docking studies have been also performed to analyze the binding mode of compounds under study and to identify the structural determinants of their interaction with both Src and Abl.
报道了新型4-氨基取代吡唑并[3,4-d]嘧啶的合成及其在Src和Abl酪氨酸激酶无细胞酶促测定中的活性。一些化合物成为这两种酶的良好双重抑制剂，对两种Bcr-Abl阳性白血病细胞系K-562和KU-812显示出抗增殖作用，并诱导细胞凋亡，如PARP测定所证明。还进行了对接研究，以分析所研究化合物的结合模式，并确定其与Src和Abl相互作用的结构决定因素。
