Design, synthesis, characterization, biological investigation and docking studies of newly synthesized sulphonyl...

Numerous medications, including non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, are available to treat inflammation. However, due to their side effects, the search for new anti-inflammatory drugs remains a major research focus. The current study addresses the synthesis, characterization of sulphonyl hydrazide, followed by in vitro and in silico analyses. Sulphonyl hydrazide compounds (R1-R5) were synthesized and characterized using physicochemical and spectroscopic methods, followed by anti-inflammatory evaluation and in silico approaches. The COX-2 and 5-LOX pathways were used for anti-inflammatory potential of compounds. The test compounds (R1-R5) showed significant activity (P < 0.05) against various in vitro enzymes. The compound R3 exhibited remarkable potency in inhibiting both COX-2 and 5-LOX, at various concentrations with IC₅₀ values of 0.84 µM and 0.46 µM, respectively. The compounds were also evaluated for their in vitro cytotoxicity in theHek293 cell line using the MTT assay to study. The synthesized compounds were further explored for in vivo anti-inflammatory potential, followed by an acute toxicity study. The compound R3 led to decreased paw edema from the 1st to 5th hour after carrageenan injection. All other compounds also showed reasonable to moderate anti-inflammatory potential. To address the compounds' mechanisms of action, they were evaluated against various phlogistic mediators, including histamine, bradykinin, leukotrienes, and prostaglandins, to confirm the anti-inflammatory pathway of the most potent synthesized compound. Their binding strategies were identified using molecular docking assays, which involved examining the interaction between the compounds and the amino acid residues in the binding pockets of the enzymes. Again, compound R3showedstrong binding affinity with the targeted receptors. The findings demonstrated that synthesized sulphonyl hydrazide complexes have significant efficacy in mitigating inflammation. Taken together, the new sulphonyl hydrazide compounds (R1-R5) elicited potential COX-2 and 5-LOX inhibition in vitro that was markedly augmented by molecular docking.