Enzymatic synthesis of novel corylifol A glucosides via a UDP-glycosyltransferase

Carbohydr Res. 2017 Jun 29:446-447:61-67. doi: 10.1016/j.carres.2017.05.002. Epub 2017 May 11.

Abstract

Corylifol A, a member of the isoflavone subclass of isoflavonoids, has long been considered to have various biological activities. Here, we sought to synthesize corylifol A glucosides by the in vitro glucosylation reaction using the UDP-glycosyltransferase YjiC from Bacillus licheniformis DSM 13, and obtained two novel glucosides: corylifol A-4',7-di-O-beta-d-glucopyranoside (1) and corylifol A-4'-O-beta-d-glucopyranoside (2). To improve the yield of the products, the reaction time, concentration of UDP-glucose, and pH of the buffer were optimized. The Michaelis constant (Km) was calculated to be 2.88 mM, and the maximal velocity (Vmax) was calculated to be 77.32 nmol/min/mg for UDP-glycosyltransferase. Meanwhile, the water-solubility of compounds 1 and 2 was approximately 27.03 and 15.13 times higher, respectively, than that of their parent compound corylifol A. Additionally, the corylifol A glycosylated products exhibited the highest stability at pH 9.6 and better temperature stability than corylifol A at 40, 60, 80 and 100 °C. In addition, cytotoxicity activity assays against three human tumor cell lines, only corylifol A showed moderate anti-proliferative activity. Overall, this work demonstrates that glycosylation can enhance the water solubility and stability of promising compounds, with potential for further development and application.

Keywords: Corylifol A; Cytotoxicity; Glycosylation; Isoflavone; Stability; Water solubility.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Bacillus licheniformis / enzymology
  • Cell Line, Tumor
  • Chemistry Techniques, Synthetic
  • Flavones / chemical synthesis*
  • Flavones / chemistry
  • Flavones / pharmacology*
  • Glucosides / chemistry*
  • Glycosyltransferases / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Solubility
  • Temperature
  • Water / chemistry

Substances

  • Antineoplastic Agents
  • Flavones
  • Glucosides
  • corylifol A
  • Water
  • Glycosyltransferases