Design, synthesis and molecular docking of new pyrazole-thiazolidinones as potent anti-inflammatory and analgesic agents with TNF-α inhibitory activity.

[Display omitted] • Synthesis of new pyrazole-methylenehydrazono-thiazolidinone derivatives 4 – 23. • In-vivo anti-inflammatory and ulcerogenic evaluation of all new compounds. • The promising derivatives were further examined as analgesics and TNF-α inhibitors. • Molecular docking of the promising compounds 5, 10, 15 and 22 was done with TNF-α. A new set of derivatives bearing pyrazole-methylenehydrazono-thiazolidinone scaffold 4 – 23 was designed, synthesized and confirmed by different spectroscopic means and elemental analyses. In-vivo anti-inflammatory and ulcerogenic evaluation was performed for all the newly synthesized derivatives using indomethacin, celecoxib and diclofenac as standard drugs. The compounds 5 , 10 , 15 , 17 , 21 , 22 appeared to be the most promising candidates producing rapid onset and long duration of anti-inflammatory activity as well as promising GIT safety profile. Furthermore, analgesic evaluation revealed that the compounds 5 , 10 , 15 and 22 produced potent and long acting analgesia accompanied with significant inhibition of the inflammatory cytokine TNF-α level in comparison with the standard drugs. Molecular docking study of the latter derivatives was also carried out to rationalize their binding affinities and their modes of interactions with the active site of TNF-α. [ABSTRACT FROM AUTHOR]