Articolo in rivista, 2016, ENG, 10.1016/j.ejmech.2016.07.034

Novel pyrazolo[3,4-d]pyrimidines as dual Src-Abl inhibitors active against mutant form of Abl and the leukemia K-562 cell line

El-Moghazy S.M.; George R.F.; Osman E.E.A.; Elbatrawy A.A.; Kissova M.; Colombo A.; Crespan E.; Maga G.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, El-kasr Elaini Street, Cairo, 11562, , , Egypt; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, El-kasr Elaini Street, Cairo, 11562, , , Egypt; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University, Beni Suef, 62511, , Egypt; Istituto di Genetica Molecolare, IGM-CNR, Via Abbiategrasso 207, Pavia, I-27100, , Italy

Some novel 6-substituted pyrazolo[3,4-d]pyrimidines 4, 5, 6a-d, 7a-c, 8 and pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidines 9a-c, 10a-c, 11, 12a,b, 13a-c and 14 were synthesized and characterized by spectral and elemental analyses. They were screened for their biological activity in vitro against Abl and Src kinases. Compounds 7a and 7b revealed the highest activity against both wild and mutant Abl kinases as well as the Src kinase and the leukemia K-562 cell line. They can be considered as new hits for further structural optimization to obtain better activity.

European journal of medicinal chemistry 123 , pp. 1–13

Keywords

Abl inhibition, K-562 cell line, Molecular modeling, Pyrazolo[3, 4-d]pyrimidines, Src inhibition

CNR authors

Maga Giovanni, Crespan Emmanuele

CNR institutes

IGM – Istituto di genetica molecolare "Luigi Luca Cavalli Sforza"