Copper Nitrate Catalyzed Synthesis Of Novel Thiazolyl Hydrazones: Anti-Inflammatory Effect Via COX-2/IL-6 Dual Antagonistic Action
Inspired by the well documented inflammation protecting ability of thiazoles, hydrazones and Schiff bases, a novel series of thiazolyl hydrazones were designed and synthesized via copper nitrate catalyzed efficient synthetic strategy. The structures of the newly synthesized compounds were elucidated based on IR, 1H NMR, 13C NMR and mass spectroscopic data. The molecular docking was conducted to elucidate the binding interactions of designed compounds with inflammation- associated targets, COX-2 (PDB ID: 3Q7D) and IL-6 (PDB ID: 1ALU). Most of compounds exhibited a stable binding complex with COX-2 and IL-6 receptors with predicted binding affinities -9.59 and -9.32, respectively. Further, the in-vivo study was investigated using the carrageenan induced paw oedema model where compounds 3b and 3f reflected a remarkable anti-inflammatory activity against diclofenac as standard drug. Interestingly, the mRNA expression analysis through qRT-PCR study further strengthened the previous findings showing the blockade of COX-2 and IL-6 mediated inflammation. Altogether, these remarkable findings open up possibilities of developing the synthesized molecules as novel candidate for plausible alternatives of NSAIDS.