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.

Effect of metal containing compounds on superoxide release from phorbol myristate acetate stimulated murine peritoneal macrophages: inhibition by auranofin and spirogermanium.

A variety of metal containing compounds were examined for their ability to inhibit the respiratory burst of murine peritoneal macrophages. Auranofin (AF), a gold containing complex used in the treatment of rheumatoid arthritis, is a potent inhibitor of the macrophage respiratory burst. Ten rhodium, iridium, osmium and ruthenium containing complexes were inactive in inhibiting superoxide production. The only active nongold organometallic complex was spirogermanium which had an equivalent IC50 for activity as AF. The inhibitory activity of AF, but not spirogermanium, was reduced in the presence of the sulfhydryl reducing agent dithiothreitol. This suggests that interactions other than those with sulfhydryl groups may be involved in the action of spirogermanium.