Highly efficient enzymatic synthesis of novel polydatin prodrugs with potential anticancer activity

Efficient lipase-mediated research work was successfully exploited for synthesizing potential 6″-O-acyl-polydatin prodrugs in biomass-derived 2-methyltetrahydrofuran (2-MeTHF). The results of the enzyme recognitions of nine acyl donors evidently demonstrated that the position and number of the C[sbnd]C double bond in acyl chains profoundly influenced the behavior of the enzyme, which could be attributable to the resonance effect between the double bond and carbonyl group. Further investigations showed that introducing various acyl groups into the polydatin apparently enhanced its pH stability and 1-octanol-water partition coefficient (log P). With regard to the human cervical cancer siHa cell apoptosis by a flow cytometry assay, the lipophilic 6″-O-sorboyl-polydatin exhibited improved apoptosis-inducing capability than the parent drug. The presence of the more lipophilic sorboyl chain in the acylated derivative could account for this.