Synthesis and Anti-tumor Activity of Ibuprofen-Coumarin Derivatives
Objective To design and synthesize new ibuprofen-coumarin derivatives to obtain new lead compounds for anti-tumor drugs with high efficiency and low toxicity.Methods According to the drug hybridization,ibuprofen-coumarin deriv-atives were synthesized using the dihydrazide (-CONHNHOC-),oxadiazole,and hydrazone bond (-CONHN=C-) as linking groups,and coumarin and ibuprofen as pharmacophores.The structure of the target compounds was characterized by1H NMR,13C NMR,and HRMS,and their anti-proliferative activity against human hepatoma cells ( HepG2) and cervi-cal cancer cells ( HeLa) was detected using the CCK-8 assay.Results Eleven target compounds were synthesized,and their 1H NMR,13C NMR,and HRMS were consistent with the predicted stuctures.The ultra-high performance liquid chromatogra-phy (UPLC) showed that the purity of the compounds was all greater than 95％.The in vitro cell activity analysis found that compound 10c had the optimal activity,with the IC50 of 5.044 μmol/L and 3.593 μmol/L against HepG2 cells and HeLa cells,respectively,which was better than ibuprofen and the commonly used anti-tumor drug gefitinib.Conclusion Ibuprofen combined with natural subactive coumarin has potential synergistic anti-tumor activity,and hydrazone groups have an impor-tant effect on the anti-tumor activity.The present study provides ideas for further structural modifications.
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