Fungal transformation of isosteviol lactone and its biological evaluation for inhibiting the AP-1 transcription factor

Phytochemistry. 2009 Apr;70(6):759-64. doi: 10.1016/j.phytochem.2009.03.015. Epub 2009 Apr 22.

Abstract

A number of hydroxylated diterpenoids were obtained from the microbial transformation of isosteviol lactone (4alpha-carboxy-13alpha-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone) (2) with Mucorrecurvatus MR 36, Aspergillusniger BCRC 31130, and Absidiapseudocylindrospora ATCC 24169. Incubation of 2 with M. recurvatus and Asp.niger led to isolation of seven known compounds (1 and 3-8). Incubation of 2 with Abs. pseudocylindrospora produced 5 and six previously unreported compounds (9-14). The structures of these isolated compounds were deduced by high-field NMR techniques ((1)H, (13)C, DEPT, COSY, NOESY, HSQC, and HMBC), and those of 9 and 11 were further confirmed by X-ray crystallographic analyses. Subsequently, the inhibitory effects on activator protein-1 (AP-1) activation in lipopolysaccharide-stimulated RAW 264.7 macrophages of all of these compounds were evaluated. Compounds 2-5, 8, 9, 11, and 12 exhibited significant inhibitory activity, while 3 was more potent than the reference compound of dexamethasone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Crystallography, X-Ray
  • Diterpenes, Kaurane / pharmacology*
  • Fungi / drug effects*
  • Lactones / pharmacology*
  • Macrophages / drug effects
  • Magnetic Resonance Spectroscopy
  • Mice
  • Models, Molecular
  • Spectrometry, Mass, Electrospray Ionization
  • Transcription Factor AP-1 / antagonists & inhibitors*

Substances

  • Diterpenes, Kaurane
  • Lactones
  • Transcription Factor AP-1
  • isosteviol lactone