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 alpha-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 IC(50) ranging from 40 to 64muM. According to ADME in silico predictions, this glycoside closely respects physicochemical parameters necessary to cross the blood-brain barrier passively.
Piochon
Marianne
M
Laboratoire d'Analyse et de Séparation des Essences Végétales (LASEVE), Département des Sciences Fondamentales, Université du Québec à Chicoutimi (UQAC), 555 boul. de l'Université, Chicoutimi, Québec, Canada G7H 2B1.
Legault
Jean
J
Gauthier
Charles
C
Pichette
André
A
D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D005643:Fucose / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
D001688:Biological Products; D005643:Fucose