Chemical Modification of the β-Glucocerebrosidase Inhibitor N-Octyl-β-valienamine: Synthesis and Biological Evaluation of 4-Epimeric and 4- O-(β- d-Galactopyranosyl) Derivatives

Abstract

N-Octyl-β-valienemine ( 1), a potent β-glucocerebrosidase inhibitor, was chemically transformed into two biologically interesting compounds: the 4-epimer 2 , β- galacto-type N-octyl-valienamine, and the 4- O-(β- d-galactopyranosyl) derivative 3 , a carba-lactosylceramide analogue. The former, interestingly, could be demonstrated to act as a very effective inhibitor (IC 50=0.3 μM) of human β-galactosidase. The latter exhibited moderate inhibitory activity (IC 50=20 μM) against β-glucocerebrosidase (mouse liver).