The molecular structure of 2alpha-hydroxyneoanisatin and structure-activity relationships among convulsant sesquiterpenes of the seco-prezizaane and picrotoxane types

Bioorg Med Chem. 1999 Dec;7(12):2857-65. doi: 10.1016/s0968-0896(99)00240-0.

Abstract

The molecular structure of 2alpha-hydroxyneoanisatin, a positional isomer of the potent neurotoxin anisatin, was determined by X-ray crystallographic analysis. This compound and four further seco-prezizaane type sesquiterpene lactones previously isolated from Illicium floridanum, which represent different structural types with respect to the mode of cyclisation, did not induce anisatin/picrotoxinin-like convulsions in mice. Based on these results and literature data for other seco-prezizaanes, structural requirements for convulsant activity are discussed. Comparison of the three dimensional molecular shape and electrostatic properties of active and inactive seco-prezizaane type lactones with compounds of the picrotoxane type resulted in the identification of a common pharmacophore structure for these different skeletal classes of convulsant natural products.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Convulsants / chemistry*
  • Convulsants / toxicity*
  • Crystallography, X-Ray
  • Male
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Neurotoxins / chemistry*
  • Neurotoxins / toxicity*
  • Plants, Toxic
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / toxicity*
  • Spiro Compounds / chemistry*
  • Spiro Compounds / toxicity*
  • Static Electricity
  • Structure-Activity Relationship

Substances

  • 2-hydroxyneoanisatin
  • Convulsants
  • Neurotoxins
  • Sesquiterpenes
  • Spiro Compounds