Anticonvulsant and Antiproteolytic Properties of 3,5-Disubstituted Oxadiazole-2-thiones and Their Inhibition of Respiration in Rat Brain Homogenates

Eight 5-(3,4-methylenedioxyphenyl)-3-arylaminomethyl-I,3,4-oxadiazole-2-thiones were synthesized, characterized by their sharp melting points, elemental analyses, and IR spectra, and evaluated for anticonvulsant activity. All substituted oxadiazole-2-thiones possessed anticonvulsant activity, which was reflected by their ability to provide 10–70% protection against pentylenetetrazol-induced convulsions in mice at 100 mg/kg ip. These compounds inhibited in vitro nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, α-ketoglu-tarate, and NADH by rat brain homogenates as well as NAD-independent oxidation of succinate by rat brain homogenates. Antiproteolytic activity of these substituted oxadiazole-2-thiones was reflected by their ability to inhibit trypsin hydrolysis of bovine serum albumin. These results indicated that the inhibition of cellular respiration and antiproteolytic activity of these substituted oxadiazole-2-thiones is not the biochemical basis for their anticonvulsant activity.