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-1,3,4-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, alpha-ketoglutarate, 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.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D051381:Rats; D014361:Trypsin Inhibitors / Q000138:chemical synthesis
D000927:Anticonvulsants; D010069:Oxadiazoles; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors