Hematopoietic cell kinase (Hck) is a member of the Src family of non-receptor protein tyrosine kinases. High levels of Hck are associated with drug resistance in chronic myeloid leukemia. Furthermore, Hck activity has been connected with HIV-1. Herein, structure-based drug design efforts were aimed at identifying novel Hck inhibitors. First, an in-house library of pyrazolo[3,4-d]pyrimidine derivatives, which were previously shown to be dual Abl and c-Src inhibitors, was analyzed by docking studies within the A K-i values ranging from 0.14 to 18.4M, confirming the suitability of the computational approach adopted. Furthermore, selected compounds showed an interesting antiproliferative activity profile against the human leukemia cell line KU-812, and one compound was found to block HIV-1 replication at sub-toxic concentrations.
Identification of Hck Inhibitors As Hits for the Development of Antileukemia and Anti-HIV Agents / Cristina, Tintori; Ilaria, Laurenzana; F., La Rocca; Federico, Falchi; Fabio, Carraro; Alba, Ruiz; Jose A., Este; Miroslava, Kissova; Emmanuele, Crespan; Giovanni, Maga; Biava, Mariangela; Chiara, Brullo; Silvia, Schenone; Maurizio, Botta. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 8:8(2013), pp. 1353-1360. [10.1002/cmdc.201300204]
Identification of Hck Inhibitors As Hits for the Development of Antileukemia and Anti-HIV Agents
BIAVA, Mariangela;
2013
Abstract
Hematopoietic cell kinase (Hck) is a member of the Src family of non-receptor protein tyrosine kinases. High levels of Hck are associated with drug resistance in chronic myeloid leukemia. Furthermore, Hck activity has been connected with HIV-1. Herein, structure-based drug design efforts were aimed at identifying novel Hck inhibitors. First, an in-house library of pyrazolo[3,4-d]pyrimidine derivatives, which were previously shown to be dual Abl and c-Src inhibitors, was analyzed by docking studies within the A K-i values ranging from 0.14 to 18.4M, confirming the suitability of the computational approach adopted. Furthermore, selected compounds showed an interesting antiproliferative activity profile against the human leukemia cell line KU-812, and one compound was found to block HIV-1 replication at sub-toxic concentrations.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
