New derivatives of ursolic acid through the biotransformation by Bacillus megaterium CGMCC 1.1741 as inhibitors on nitric oxide production

Bioorg Med Chem Lett. 2017 Jun 1;27(11):2575-2578. doi: 10.1016/j.bmcl.2017.03.076. Epub 2017 Mar 27.

Abstract

Microbial transformation of ursolic acid (1) by Bacillus megaterium CGMCC 1.1741 was investigated and yielded five metabolites identified as 3-oxo-urs-12-en-28-oic acid (2); 1β,11α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3); 1β-hydroxy-3-oxo-urs-12-en-28, 13-lactoe (4); 1β,3β, 11α-trihydroxyurs-12-en-28-oic acid (5) and 1β,11α-dihydroxy-3-oxo-urs-12-en-28-O-β-d-glucopyranoside (6). Metabolites 3, 4, 5 and 6 were new natural products. Their nitric oxide (NO) production inhibitory activity was assessed in lipopolysaccharide (LPS) - stimulated RAW 264.7 cells. Compounds 3 and 4 exhibited significant activities with the IC50 values of 1.243 and 1.711μM, respectively. A primary structure-activity relationship was also discussed.

Keywords: Bacillus megaterium CGMCC 1.1741; Microbial transformation; Nitric oxide production; Ursolic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacillus megaterium / metabolism*
  • Lipopolysaccharides / toxicity
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Conformation
  • Nitric Oxide / metabolism
  • RAW 264.7 Cells
  • Structure-Activity Relationship
  • Triterpenes / chemistry
  • Triterpenes / metabolism*
  • Triterpenes / pharmacology
  • Ursolic Acid

Substances

  • Lipopolysaccharides
  • Triterpenes
  • Nitric Oxide