Synthesis and Antioxidant Properties of Novel 2-(2,4-Dioxothiazolidin-5-ylidene)-Acetamides Containing 1,3,4-Thia/Oxadiazole Moieties

A series of novel 1,3,4-thia(oxa)diazole substituted 2-(2,4-dioxothiazolidine-5-ylidene)-acetamides3a-c, 4 and 5a-k have been synthesized following the acylation reaction of 2-amino-5-aryl-1,3,4-oxadiazoles,5-amino-1,3,4-thiadiazole-2-thiol and it's S-alkylated derivatives with 2-(2,4-dioxothiazolidine-5-ylidene)acetylchloride in dioxane medium. The functionalization of compounds 3b, 3c, 5d and 5e was carried out on their N-3 position under N-alkylation conditions with N-aryl-2-chloroacetamidesin DMF/ethanol medium yielded the corresponding 2,4-dioxothiazolidine-3,5-diaceticacid diamides 6a-e and 7a-b. The structures of target compounds were confirmed by using (HNMR)-H-1 spectroscopy and elemental analysis. The antioxidant activity evaluation in vitro of the synthesized compounds was performed by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. As a result, the highly active compound 4, namely 2-(2,4-dioxothiazolidin-5-ylidene)-N-(5-mercapto-[1,3,4]thiadiazol-2-yl)acetamidewas found to be the most efficient candidate among all compounds with a radical scavenging ability of 88.9%, which was comparable that for ascorbic acid (92.7%). The experimentally calculated IC50 value of 43.1 mu M for compound 4 was lower than for ascorbic acid (50.5 mu M).