Efficient enzymatic synthesis and antibacterial activity of andrographolide glycoside

• Enzymatic galactosylation of andrographolide in co-solvents was carried out.
• β-Galactosidase displayed high regioselectivity and stability in 5–15% DMSO–PBS.
• Andrographolide glycoside has higher solubility in water than andrographolide.
• Antibacterial activities of glycoside were higher than those of andrographolide.

19-O-β-Galactosyl andrographolide, a potential novel antibacterial agent, was synthesized through enzymatic transgalactosylation of andrographolide in co-solvent systems. Organic solvents and their contents have important influences on the regioselective galactosylation of andrographolide catalyzed by β-galactosidase from bovine liver in co-solvent systems. β-Galactosidase showed high activity and stability in 5–15% (v/v) DMSO with 22–52% total molar yields of andrographolide glycosides. The addition of hydrophilic DMSO not only greatly promoted the solubility of the substrate, but also improved the reaction efficiency of the process. β-Galactosidase displayed absolute regioselectivity toward the 19-position of andrographolide. The solubility of andrographolide glycoside in water was 42.1 mg ml−1, which is about 702 times that of andrographolide. The glycosylated andrographolide showed antibacterial activity against five representative species of food-borne pathogenic bacteria [with minimal inhibitory concentrations (MICs) as low as 8 μg ml−1], whereas andrographolide exhibited no such activity. These results indicate an enzymatic modification was not only facile and green, but an effective method for the preparation of an andrographolide monoglycoside.

Enzymatic regioselective galactosylation of andrographolide catalyzed by β-galactosidase from bovine liver.Figure optionsDownload as PowerPoint slide