Synthesis and cytotoxicity evaluation of natural α-bisabolol β-d-fucopyranoside and analogues

Abstract α-Bisabolol β- d -fucopyranoside, a cytotoxic naturally occurring compound, was efficiently synthesized along with five other α-bisabolol glycosides (β- d -glucoside, β- d -galactoside, α- d -mannoside, β- d -xyloside and α- l -rhamnoside). Glycosidation of α-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 α-bisabolol was previously demonstrated against brain tumor cell lines. The addition of a sugar moiety markedly increased α-bisabolol cytotoxicity in most cases. Among the synthesized glycosides, α-bisabolol α- l -rhamnopyranoside exhibited the strongest cytotoxic activity with IC 50 ranging from 40 to 64 μM. According to ADME in silico predictions, this glycoside closely respects physicochemical parameters necessary to cross the blood–brain barrier passively.