synthesis, biological evaluation and molecular docking studies of ferrocene derivatives coupling with n-heterocyclic on human breast cancer

A series of heterocyclic ferrocene derivatives (Fc1–Fc18) was designed and synthesized. The eight representative target compounds were evaluated for their antitumor activities against human breast cancer (MCF-7) cells using MTT assay. Compounds Fc3, Fc11, Fc12, and Fc17 inhibited MCF-7 cells at IC50 values of 39.2, 44.2, 48.3, and 24.2 (μmol/L). In the eight heterocyclic ferrocene derivatives, results indicated that they had a pyridine group and produced ester which is more effective in inhibiting MCF-7 cells than that of amide-producing heterocyclic ferrocene derivatives without a pyridine group. Docking simulation was also performed to position compounds into the human enzyme aromatase (AR, CYP19) active site adequately to explain the probable reasons why the compounds have antitumor activities. The authors observed that compound Fc17, which had the highest affinity to the receptor, was stabilized by two respective hydrogen bonds with Thr310 and Ser314.