Potent Anticonvulsant Paeonimetabolin-I Derivatives Obtained by Incubation of Paeoniflorin and Thiol Compounds with Lactobacillus brevis

Abstract

Seventeen thiopaeonimetabolin-I adducts were obtained as mixtures of diastereoisomers after incubation of paeoniflorin with Lactobacillus brevis in the presence of various thiols. Four compounds, 8-(n-hexylthio)- (8), 8-cyclopentylthio-, 8-(p-tolyl)thio- and 8-benzoylthio- (18) paeonimetabolins, showed 100% protection against pentylenetetrazole-induced convulsions at doses of 0.125, 0.25, or 0.50 mmol/kg, relative to valproic acid (100% protection at 1.5 mmol/kg). For 8 and 18, the principle anticonvulsant activity resided in the (7S)-isomers while (7R)-isomers showed muscle relaxation effects.