Crystal structure and anticonvulsant activity of (+/-)-1,2:4,5-di-O-isopropylidene-3,6-di-O-(2-propylpentanoyl)-myo-inositol.
The biological activity and crystal structure of (+/-)-1,2:4,5-di-O-isopropylidene-3,6-di-O-(2-propylpentanoyl)-myo-inositol have been investigated. This compound shows better anticonvulsant activity than valproic acid (VPA) in the MES test as measured in mice. Its structure, determined from single-crystal X-ray diffraction measurements, shows that the inositol ring deviates from the ideal chair conformation and that the two 2-propylpentanoyl groups are located on opposite ring positions. This molecular conformation lets carbonyl and hydroxyl oxygen atoms to be available for hydrogen-bonding interactions, hinders carbonyl carbon atoms, preventing metabolic enzymatic hydrolysis, and helps to rationalize the observed inactive profile in the PTZ test. The anticonvulsant activity profile suggests a mechanism different from that of VPA.
Moon
Sung C
SC
Cátedra de Química Medicinal, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Calle 47 y 115 s/n. B1900AVV, La Plata, Argentina.
Echeverría
Gustavo A
GA
Punte
Graciela
G
Ellena
Javier
J
Bruno-Blanch
Luis E
LE
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry*; D002236:Carbohydrate Conformation; D018360:Crystallography, X-Ray; D004597:Electroshock; D007294:Inositol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D051379:Mice; D010433:Pentylenetetrazole / Q000008:administration & dosage; D014635:Valproic Acid / Q000008:administration & dosage / Q000737:chemistry
C452020:1,2-5,6-di-O-isopropylidene-myo-inositol; D000927:Anticonvulsants; D007294:Inositol; D014635:Valproic Acid; D010433:Pentylenetetrazole