Design, synthesis and molecular docking study of coumarin pyrazoline derivatives against MCF-7 breast cancer cell line

A new eight series of 3-(2-oxo-2H-chromen-3-yl)-5-(substituted phenyl)-1H-pyrazole-1-carbaldehyde derivatives (9-16) were designed and created from coumarin-chalcone derivatives (1-8). The structures of the derivatives were established by using melting point, mass spectrum, IR, (HNMR)-H-1, and C-13 NMR spectroscopic methods. In vitro antiproliferative activities were evaluated against MCF-7 breast cancer cell line using Microculture Tetrazolium (MTT) assay. The results showed that the compounds 9, 12- 14 has a moderate activity against MCF-7 breast cancer cell line with IC50 61.44, 70.11, 22.6 and 25.99 mu g/mL respectively, while the compounds 10,11, 15 and 16 were found to be inactive against studied cell line within IC50 > 100 mu g/mL. The possible binding interaction between studied compounds (9-16) and human ER-a (PDB ID: 1ERR) were studied by molecular docking. The results revealed that only the compounds 11 and 16 form p -H interaction with ER-alpha (PDB ID: 1ERR) within the highest negative values of binding affinity -7.04260 and -7.17308 kcal.mol(-1) respectively than the other compounds, while Raloxifene used here as a positive control form a strong ionic bonding with Asp 351 within the binding affinity -9.61928 kcal/mol which is more negative value than the studied compounds.