Substituted thiazolidones: selective inhibition of nicotinamide adenine dinucleotide-dependent oxidations and evaluation of their CNS activity

• Published in: Journal of pharmaceutical sciences Vol. 64; no. 4; p. 614
• Main Authors: Chaudhari, S K, Verma, M, Chaturvedi, A K, Parmar, S S
• Format: Journal Article
• Language: English
• Published: United States 01-04-1975
• Subjects: Animals; Anticonvulsants - pharmacology; Behavior, Animal - drug effects; Brain - drug effects; Brain - metabolism; Drug Synergism; Lethal Dose 50; Male; NAD - antagonists & inhibitors; Oxidation-Reduction; Pentobarbital - pharmacology; Rats; Thiazoles - pharmacology; Thiazoles - toxicity
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600640408

Eight 2-arylimino-3-(3-N-morpholinopropyl) thiazolid-4-ones were synthesized from the corresponding 1-aryl-3-(3-N-morpholinopropyl) thiocarbamides, characterized, and tested for their effects on the cellular respiratory activity of rat brain homogenates. All substituted 4-thiazolidones selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidations of pyruvate, citrate, DL-isocitrate, alpha-ketoglutarate, malate, beta-hydroxybutyrate, L-glutamate, and NADH, while the NAD-independent oxidation of succinate remained unaltered. All thiazolidones possessed some degree of anticonvulsant activity against pentylenetetrazol-induced convulsions, and the protection afforded by these compounds at a dose of 100 mg/kg ranged from 30 to 80%. The low toxicity possessed by most of these thiazolidones was reflected by their approximate LD-50 values from 300 mg/kg to greater than 1000 mg/kg. In the present study, the anticonvulsant activity possessed by these substituted 4-thiazolidones was unrelated to their ability to inhibit selectively the NAD-dependent oxidations by rat brain homogenates. These thiazolidones exhibited depression of the CNS activity which, in some cases, was associated with the increase in respiration. All thiazolidones potentiated pentobarbital (sodium) sleeping time in mice when administered in a dose of 100 mg/kg.