Synthesis, characterization and antitumor activity of novel ferrocene-coumarin conjugates

Abstract

Seven novel ferrocene-coumarin conjugates, namely FcL1~FcL7, were synthesized and confirmed by 1H NMR, FT-IR, elemental analysis. The crystal structure of FcL3 was determined by X-ray diffraction, showing that the dihedral angle between the coumarin and the substituted cyclopentadienyl ring was 80.67°. The electrochemical behaviors of FcL1~FcL7 exhibited similar quasireversible redox waves, while the formal potential E0 values of FcL1~FcL5 were distinctively lower than FcL6 and FcL7 due to electronic-effect of substituents. Notably, the title compounds, when screened on human tumor cell lines (MCF-7, BIU-87, SGC-7901, EC-9706, Eca-109 and Jurkat), exhibited potent and broad spectrum activities. Among them, FcL1~FcL5 exhibited more toxicity to most cancer cell lines than FcL6 and FcL7 because of the lower E0. Remarkably, FcL4 showed significant in vitro cytostatic effect on BIU-87 cell line giving respective IC50 values of 1.09 μmol/L, which was much better than that of Adriamycin (IC50 = 6.09 μmol/L). The cytotoxicity assay against SGC-7901 cells also revealed that the complex FcL5 (IC50 = 3.56 μmol/L) was superior to the reference drug Adriamycin (IC50 = 5.44 μmol/L). Consequently, ferrocene-coumarin conjugates are potential candidates for developing metallodrugs with impressive anticancer activity.