Synthesis, characterization, molecular docking and in vitro anti-arthritic activity of some novel spiro 1,3,4 thiadiazole derivatives based on thioxoacetamides

Abstract A new series of spiro1,3,4thiadiazole derivatives based on thioxoacetamides were synthesized, characterized, and evaluated for anti-arthritic potential. The structures of all compounds ( 2a–12a ) were confirmed using IR, NMR, and elemental analysis. In vitro anti-arthritic activity was assessed via protein denaturation inhibition and RBC membrane stabilization assays. Compounds 9a , 10a , 6a , 6b , 6c , and 6d showed superior activity compared to the standard drug indomethacin, with 9a being the most potent (IC₅₀ = 29.6 µg/mL for protein denaturation). Molecular docking against COX-2 (PDB: 5IKT) revealed strong binding affinities, especially for 9a (− 8.59 kcal/mol), 10a (− 8.45 kcal/mol), and 6a (− 8.05 kcal/mol). DFT studies indicated favorable electronic properties comparable to indomethacin. These results highlight the promising anti-arthritic potential of the synthesized spirothiadiazole derivatives. Graphical Abstract