Results from molecular docking calculations and Grid mapping laid the foundations for a structure-based optimization approach to improve the biological properties of pyrazolo-pyrimidine derivatives in terms of inhibition of Abl enzymatic activity and antiproliferative properties toward human leukemia cells. Insertion of halogen substituents with various substitution patterns, suggested by simulations, led to a significant improvement of leukemia cell growth inhibition and to an increase up to 1 order of magnitude of the affinity toward Abl.
|Autori:||MANETTI F; BRULLO C; MAGNANI M; MOSCI F; CHELLI B; CRESPAN E; SCHENONE S; NALDINI A; BRUNO O; TRINCAVELLI ML; MAGA G; CARRARO F; MARTINI C; BONDAVALLI F; BOTTA M|
|Titolo:||Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines|
|Anno del prodotto:||2008|
|Digital Object Identifier (DOI):||10.1021/jm701240c|
|Appare nelle tipologie:||1.1 Articolo in rivista|