Antihemolytic and anticonvulsant activities of 1-(2,4-dichloro/2,4,5-trichlorophenoxyacetyl)-4-alkyl/arylthiosemicarbazides and their inhibition of NAD-dependent oxidations and monoamine oxidase.
Several 1-(2,4-dichloro and 2,4,5-trichlorophenoxyacetyl)-4-alkyl/arythiosemicarbazides were synthesized and characterized by their sharp melting points and elemental analyses. All substituted thiosemicarbazides protected in vitro hypoosmotic hemolysis of dog red blood cells. These thiosemicarbazides selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate and alpha-ketoglutarate, while NAD-independent oxidation of succinate was not affected. These compounds inhibited the activity of monamine oxidase in rat brain homogenate, and the degree of inhibition ranged from 26.5 to 89.2 percent at a final concentration of 0.03mM, with kynuramine as the substrate. Almost all thiosemicarbazides possessed anticonvulsant activity; protection against pentylenetetrazol-induced convulsions in mice ranged from 10 to 70 percent at a dose of 100 mg/kg ip. These results provided evidence of some similarity between the membrane-stabilizing property of these substituted thiosemicarbazides with their ability to exhibit selective inhibition of NAD-dependent oxidations and inhibition of monoamine oxidase. On the other hand, the anticonvulsant activity possessed by these substituted thiosemicarbazides was unrelated to their in vitro antihemolytic and enzyme inhibitory properties.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003864:Depression, Chemical; D005260:Female; D006461:Hemolysis / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D051381:Rats; D013882:Thiosemicarbazones / Q000494:pharmacology*
D000927:Anticonvulsants; D008996:Monoamine Oxidase Inhibitors; D013882:Thiosemicarbazones; D009247:NADH, NADPH Oxidoreductases