Synthesis, computational study and cytotoxic activity of new 4-hydroxycoumarin derivatives

Six new 4-hydroxycoumarin derivatives have been synthesized. They were characterized by UV–vis, IR, 1H NMR, 13C NMR, mass spectral data, elemental analysis, TLC and melting point determination. The new 4-hydroxycoumarin derivatives are studied by computational methods – DFT (B3LYP) and force field methods (MM2 and OPLS), in order to optimize their geometry and calculate quantum-chemical properties and conformational analysis. Five new 4-hydroxycoumarin derivatives were tested for cytotoxic activity in two tumor cell lines – HL-60 and EJ. The obtained results are compared with the utilized anticancer drug melphalan. Two of these compounds – ethyl 2-[(3,4-dihydroxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-3-oxobutanoate (SS-16) and ethyl 2-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(3-nitrophenyl)methyl]-3-oxobutanoate (SS-21) show comparatively good cytotoxic properties. Their activity is weaker than melphalan. SS-16 seems to be more active than SS-21.

Six new coumarin derivatives have been synthesized. They are studied by computational methods and for in vitro cytotoxic activity. The most active is ethyl 2-[(3,4-dihydroxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-3-oxobutanoate (SS-16).Figure optionsDownload as PowerPoint slide