Lipase-catalyzed synthesis mechanism of tri-acetylated phloridzin and its antiproliferative activity against HepG2 cancer cells.

Abstract

Herein, we perform the regioselective acetylation of phloridzin catalyzed by immobilized Candida antarctica lipase B (CALB). We show that the enzyme amount and reaction time can significantly influence the composition of mono-, di- and tri-acetylated phloridzin in the product. The last acetylated derivative of phloridzin is isolated and identified as 4, 3″, 6″-3-O-acetyl-phloridzin by HPLC, UV, IR, MS and NMR. Molecular docking suggests that the first acetylation of phloridzin catalyzed by CALB occurs in 6″-OH, followed by 3″-OH, then 4-OH. During this process, hydrogen bond and hydrophobic forces play an important role in maintaining the binding interaction of CALB with phloridzin or its acetylated derivatives. Although, tri-acetylated phloridzin has moderate to minimal adverse-effects on LO-2, its anti-proliferative activity against human HepG2 cancer cells is superior to that of phloridzin, which attributes to its high capacity of inducing cell apoptosis, retarding cell cycle, lowering mitochondrial membrane potential and scavenging intracellular ROS.

• Authors: Yongsheng Chen, Jiangwei Liu, Sheng Geng, Yonglan Liu, Hanjun Ma, Jie Zheng, Benguo Liu, Guizhao Liang
• Journal: Food chemistry (Food Chem) Vol. 277 Pg. 186-194 (Mar 30 2019) ISSN: 1873-7072 [Electronic] England
• PMID: 30502134 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Enzymes, Immobilized
• Fungal Proteins
• Phlorhizin
• Lipase
• lipase B, Candida antarctica

Topics

• Acetylation
• Antineoplastic Agents (chemical synthesis, chemistry, metabolism, pharmacology)
• Apoptosis (drug effects)
• Biocatalysis
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Enzymes, Immobilized (chemistry, metabolism)
• Fungal Proteins (chemistry, metabolism)
• Humans
• Lipase (chemistry, metabolism)
• Molecular Docking Simulation
• Phlorhizin (chemical synthesis, chemistry, metabolism, pharmacology)