Potent anticonvulsant paeonimetabolin-I derivatives obtained by incubation of paeoniflorin and thiol compounds with Lactobacillus brevis.
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.
Abdel-Hafez
A A
AA
Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, Japan.
Meselhy
M R
MR
Nakamura
N
N
Hattori
M
M
Watanabe
H
H
Mohamed
T A
TA
Mahfouz
N M
NM
el-Gendy
M A
MA
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000627:therapeutic use; D001565:Benzoates; D001952:Bridged-Ring Compounds; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000737:chemistry*; D007778:Lactobacillus / Q000378:metabolism*; D008297:Male; D051379:Mice; D039821:Monoterpenes; D010433:Pentylenetetrazole; D010946:Plants, Medicinal; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014635:Valproic Acid / Q000627:therapeutic use; D006027:Glycosides
D000927:Anticonvulsants; D001565:Benzoates; D001952:Bridged-Ring Compounds; D005960:Glucosides; D039821:Monoterpenes; D010433:Pentylenetetrazole; D013438:Sulfhydryl Compounds; D014635:Valproic Acid; C015423:peoniflorin; D006027:Glycosides