Synthesis and in vivo evaluation of novel thiadiazoles as carbonic anhydrase inhibitors to attenuate inflammation-induced thermal hyperalgesia in irradiated Rats

Abstract

New series of thiadiazole derivatives (2-8) and thiadiazolo[3,2-a]pyrimidines (15-17) were synthesized from the starting compound (1) 5-amino-1,3,4-thiadiazole-2(3H)-thione. The structures of these compounds were confirmed by elemental analysis, IR, ¹H-NMR and ¹³C-NMR spectral data. The compounds were tested against inflammation-induced hyperalgesia caused by intramuscular injection of carrageenan in rats. After administration of each of the thiadiazoles to irradiated inflamed rats; the inflammation-induced hyperalgesia, carbonic anhydrase activity, antioxidant effect and lactate dehydrogenase activity, were measured. To reveal the possible mechanism(s) of action of the most promising compounds (3, 9 and 10); we tested their antioxidant, anti-inflammatory and the central analgesic effects and they showed promising results. These compounds reduced inflammation-induced hyperalgesia, probably by acting centrally and peripherally.