Synthesis and cytotoxicity evaluation of natural alpha-bisabolol beta-D-fucopyranoside and analogues

alpha-Bisabolol beta-D-fucopyranoside, a cytotoxic naturally occurring compound, was efficiently synthesized along with five other alpha-bisabolol glycosides (beta-D-glucoside, beta-D-galactoside, alpha-D-mannoside, beta-D-Xyloside and alpha-L-rhamnoside). Glycosidation of ot-bisabolol was performed using Schmidt's inverse procedure and provided excellent yields (83-95%). Cytotoxicity was evaluated against a broad panel of cancerous cell lines including human and rat glioma (U-87, U-251 and GL-261) since the anticancer activity of alpha-bisabolol was previously demonstrated against brain tumor cell lines. The addition of a sugar moiety markedly increased alpha-bisabolol cytotoxicity in most cases. Among the synthesized glycosides, alpha-bisabolol alpha-L-rhamnopyranoside exhibited the strongest cytotoxic activity with IC50 ranging from 40 to 64 mu M. According to ADME in silico predictions, this glycoside closely respects physicochemical parameters necessary to cross the blood-brain barrier passively. (C) 2008 Elsevier Ltd. All rights reserved.