Novel thiadiazole derivatives: synthesis, in silico, in vitro and in vivo evaluation of analgesic and anti-inflammatory activities.

Pain and inflammation are closely linked pathophysiological processes contributing to numerous diseases. However, current pharmacological treatments are limited by adverse effects and incomplete efficacy, underscoring the need for safer alternatives. Thiadiazole derivatives have emerged as promising candidates due to their broad biological activities and cyclooxygenase-2 (COX-2) inhibitory potential. In this study, six novel thiadiazole derivatives (4a-4f) were synthesized and initially evaluated by molecular docking. Based on docking scores comparable to celecoxib, three compounds (4d, 4e, 4 f) were selected for in vivo pharmacological testing. Central analgesic activity was assessed using the hot-plate and tail-immersion tests, peripheral analgesic effects were evaluated by the acetic acid-induced writhing test, and anti-inflammatory properties were investigated in the carrageenan-induced paw edema model. Compounds 4d, 4e, and 4 f significantly prolonged reaction times in thermal nociception assays and attenuated writhing responses, indicating both central and peripheral analgesic activity. In the paw edema model, all three derivatives effectively reduced inflammation. Molecular docking analyses further confirmed stable COX-2 binding interactions, supporting their selective inhibitory potential. Collectively, these findings suggest that the newly synthesized thiadiazole derivatives hold potential as analgesic and anti-inflammatory drug candidates and needs to be evaluated through comprehensive preclinical and clinical studies in future.