Piochon Marianne, Legault Jean, Gauthier Charles, Pichette André
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.
Phytochemistry. 2009 Jan;70(2):228-36. doi: 10.1016/j.phytochem.2008.11.013. Epub 2009 Jan 10.
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.
α-红没药醇β-D-呋喃岩藻糖苷，一种具有细胞毒性的天然化合物，与其他五种α-红没药醇糖苷（β-D-葡萄糖苷、β-D-半乳糖苷、α-D-甘露糖苷、β-D-木糖苷和α-L-鼠李糖苷）一起被高效合成。α-红没药醇的糖基化反应采用施密特逆合成法进行，产率优异（83-95%）。鉴于先前已证明α-红没药醇对脑肿瘤细胞系具有抗癌活性，因此针对包括人源和大鼠源胶质瘤（U-87、U-251和GL-261）在内的多种癌细胞系评估了其细胞毒性。在大多数情况下，糖基部分的添加显著增强了α-红没药醇的细胞毒性。在合成的糖苷中，α-红没药醇α-L-鼠李吡喃糖苷表现出最强的细胞毒性活性，IC50范围为40至64μM。根据计算机模拟的ADME预测，该糖苷非常符合被动穿过血脑屏障所需的物理化学参数。
