Anti-inflammatory and analgesic effect of LD-RT and some novel thiadiazole derivatives through COX-2 inhibition

Generally, highly selective COX-2 inhibitors cause cardiovascular side effects. Celecoxib is the highly marketed coxib, so there is still a need for the synthesis of COX-2 inhibitors with less adverse effects. Moreover, low-dose radiotherapy (LD-RT) is clinically used for the treatment of inflammatory diseases. The present study aimed to investigate the analgesic and anti-inflammatory activity of a novel series of 1,3,4-thiadiazole derivatives alone or combined with LD-RT with a single dose of 0.5 Gy. Initially, in vitro COX-1/COX-2 inhibition assays were performed, identifying the sulfonamide-containing compounds 5 – 10 as the most potent candidates, with IC₅₀ values in the range of 0.32–0.37 µM and the highest selectivity indices. These compounds and celecoxib were subjected to in vivo examination after their safety was assessed through the acute toxicity test. Treatment with compounds 5 – 10 inhibited carrageenan-induced edema by nearly 47–56%, which was nearly equivalent to celecoxib. Compounds 7 and 8 and celecoxib showed an analgesic activity of 64.15%, 49.05%, and 84.90%, respectively, whereas compounds 5 , 6 , 9 , and 10 did not show any analgesic activity unless combined with LD-RT. Ulcerogenic activity, histological paw examination, and docking studies were performed. Compounds 5 – 10 were nearly similar to celecoxib, showing normal histological features with no ulcerogenic activity.