The molecular structure of 2alpha-hydroxyneoanisatin and structure-activity relationships among convulsant sesquiterpenes of the seco-prezizaane and picrotoxane types.
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.
Schmidt
T J
TJ
Institut für Pharmazeutische Biologie der Heinrich-Heine-Universität Düsseldorf, Germany. schmidt@uni-duesseldorf.de
Okuyama
E
E
Fronczek
F R
FR
D000818:Animals; D003292:Convulsants / Q000737:chemistry* / Q000633:toxicity*; D018360:Crystallography, X-Ray; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009498:Neurotoxins / Q000737:chemistry* / Q000633:toxicity*; D010947:Plants, Toxic; D012717:Sesquiterpenes / Q000737:chemistry* / Q000633:toxicity*; D013141:Spiro Compounds / Q000737:chemistry* / Q000633:toxicity*; D055672:Static Electricity; D013329:Structure-Activity Relationship
C405339:2-hydroxyneoanisatin; D003292:Convulsants; D009498:Neurotoxins; D012717:Sesquiterpenes; D013141:Spiro Compounds