Anticonvulsant and antiproteolytic properties of 2,5-disubstituted oxadiazoles and their inhibition of respiration in rat brain homogenates.
Eight 2-(3,4-methylenedioxyphenyl)-5-arylamino1,3,4-oxadiazoles were synthesized, characterized by their sharp melting points, elemental analyses, and IR spectra, and evaluated for anticonvulsant activity. The protection afforded by oxadiazoles (100 mg/kg ip) against pentylenetetrazol (90 mg/kg sc)-induced convulsions ranged from 50 to 80%. All oxadiazoles inhibited the respiratory activity of rat brain homogenates during oxidation of pyruvate, alpha-ketoglutarate, and succinate. The presence of added nicotinamide adenine dinucleotide (NAD) to the reaction mixture during oxidation of pyruvate decreased the degree of inhibition. All oxadiazoles possessed antiproteolytic activity that was reflected by their ability to decrease trypsin-induced hydrolysis of bovine serum albumin. Such an inhibition was concentration dependent and ranged from 10.2 to 47.5 and from 15.7 to 71.8% by 0.5 and 1 mM oxadiazoles, respectively. All oxadiazoles competitively inhibited in vitro succinate dehydrogenase activity of rat brain homogenates.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007656:Ketoglutaric Acids / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013386:Succinates / Q000378:metabolism
D000927:Anticonvulsants; D007656:Ketoglutaric Acids; D010069:Oxadiazoles; D011773:Pyruvates; D013386:Succinates; D012710:Serum Albumin, Bovine