Design, Synthesis and Evaluation of Pentacyclic Triterpenoids Similar to Glycyrrhetinic Acid Via Combination of Chemical and Microbial Modification as Glycogen Phosphorylases Inhibitor

J Microbiol Biotechnol. 2018 Nov 28;28(11):1876-1882. doi: 10.4014/jmb.1804.04042.

Abstract

A series of pentacyclic triterpenoids similar to glycyrrhetinic acid were designed and synthesized via the combination of chemical modification and microbial catalysis. All products were screened for the glycogen phosphorylases inhibitory activities in vitro. Within this series of derivatives, compound 5 displayed good inhibitory activities with IC50 value of 27.7 μM, which is better than that of the other derivatives and glycyrrhetinic acid. Structure-activity relationship (SAR) analysis of these inhibitors was also discussed.

Keywords: Aspergillus ochraceus CICC 40330; Biocatalysis; Streptomyces griseus ATCC 13273; glycyrrhetinic acid; oleanolic acid.

MeSH terms

  • Aspergillus ochraceus / metabolism*
  • Biotransformation
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Glycogen Phosphorylase / antagonists & inhibitors*
  • Glycyrrhetinic Acid / analogs & derivatives
  • Glycyrrhetinic Acid / chemistry
  • Inhibitory Concentration 50
  • Molecular Structure
  • Oleanolic Acid* / biosynthesis
  • Oleanolic Acid* / chemical synthesis
  • Oleanolic Acid* / chemistry
  • Oleanolic Acid* / metabolism
  • Streptomyces griseus / metabolism*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Oleanolic Acid
  • Glycogen Phosphorylase
  • Glycyrrhetinic Acid