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Highly efficient enzymatic synthesis of novel polydatin prodrugs with potential anticancer activity
Affiliation:1. School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai’an 223003, China;2. College of Food Science and Light Industry, Nanjing Tech University, Nanjing 211816, China;3. School of Medicine, Yunnan University, Kunming 650091, China;1. University of Belgrade, Faculty of Technology and Metallurgy, Karnegijeva 4, Belgrade, Serbia;2. University of Belgrade, Faculty of Agriculture, Nemanjina 6, Belgrade, Serbia;1. Key Laboratory of Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130012, China;2. College of Life Science, Jilin University, Changchun 130012, China;3. The First Hospital of Jilin University, Changchun 130021, China;1. Institute of Agricultural Products Processing, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, PR China;2. College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, PR China;3. Ginling College, Nanjing Normal University, Nanjing 210024, PR China;4. Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing Agricultural University, Nanjing 210095, PR China;1. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;2. Department of Anesthesiology, Taipei Tzu Chi Hospital, New Taipei City, Taiwan;3. School of Medicine, Tzu Chi University, Hualien, Taiwan
Abstract: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 Csingle bondC 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.
Keywords:Polydatin  Enzymatic acylation  Acyl recognition  Cell apoptosis  2-Methyltetrahydrofuran
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