Efficient enzymatic synthesis and antibacterial activity of andrographolide glycoside

Abstract

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 42.1mgml−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 8μgml−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.