β-Secretase (BACE1) has been widely recognized as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the BACE1 inhibitory activity of new, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides. Each enantiomeric form was separately evaluated in BACE1 inhibition assays and IC(50) values were obtained in the low micromolar range. According to our biological results and docking studies, it can be asserted that the stereochemistry around the OH group in the central hydroxyethylamino linker does not significantly influence the BACE1 inhibitory activity of this type of molecules.
BACE1 inhibitory activities of enantiomerically pure, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides
BERTINI, SIMONE;GRANCHI, CARLOTTA;MINUTOLO, FILIPPO;PINESCHI, MAURO;DI BUSSOLO, VALERIA;SABA, ALESSANDRO;MACCHIA, MARCO
2010-01-01
Abstract
β-Secretase (BACE1) has been widely recognized as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the BACE1 inhibitory activity of new, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides. Each enantiomeric form was separately evaluated in BACE1 inhibition assays and IC(50) values were obtained in the low micromolar range. According to our biological results and docking studies, it can be asserted that the stereochemistry around the OH group in the central hydroxyethylamino linker does not significantly influence the BACE1 inhibitory activity of this type of molecules.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
