Design, molecular docking studies of oxaprozin linked to 4-Thiazolidinone derivatives as a potent anticancer, analgesic and antiinflammatory agents

In the present study, we introduced acyl hydrazone derivatives of 3-(4, 5-diphenyl-1, 3-oxazol-2-yl) propanoic acid as new potent and selective anticancer, analgesic and anti inflammatory inhibitors that lack the standard pharmacophoric binding features to PDBID 2ZCS. The key intermediate N-acyl hydrazine is prepared in good yields from oxaprozin, was integrate with a variety of aromatic aldehydes under conventional conditions. The newly synthesized compounds have been characterized by IR, 1H NMR, 13C NMR and Mass spectral analysis. Further, the compounds 5a, 5b, 5e, 5g, and 5h announce promising invitro cytotoxicity than reference compound cisplatin. All the target compounds have been screened for their invivo anti-inflammatory activity on rats by carrageenan-induced ratpaw edema assay. The results of the biological activities showed that the compounds 5b, 5d and 5e exhibited significant invivo analgesic and anti inflammatory activities than reference compound oxaprozin. Further investigation, starting from our lead compound 5i, structure-based drug-design was conducted and more potent analogues were obtained with high selectivity and almost full edema protection, in carrageenan-induced autodock 4.2, in case of compounds 5a, 5g, 5d and 5e showed the good binding energy by adding a substituted phenyl rings afforded excellent active compounds. The activity data is validated by molecular docking studies and are in good corelation with observed trends.