Synthesis And Antitumor Activity Evaluation Of Ferrocene Amide Derivatives

Ferrocene has attracted special attention since its discovery in the early 1950s. Because it is neutral, chemically stable, non-toxic, anomalous metabolism and membrane-permeation properties, people have exploited a large number of ferrocenyl derivatives. Ferrocene and its derivatives have been widely applied in numerous research fields, including catalysis in organic synthesis, biochemistry and medicine, electrochemical and photoelectric functional materials, organometallic chemistry, supramolecular assembly and ion sensor. They have various biological functions in biotechnology areas, such as antitumor, anti-anemia, anti-malaria, sterilization, regulation of plant growth and so on.In this paper, ferrocenecarboxaldehyde and acetylferrocene were used as raw material, designed and synthesized two series of new ferrocenyl derivatives. The structures of these compounds were comfirmed by 1H NMR,13C NMR, MS and elemental analysis. Furthermore, four compounds among them were also characterized by X-ray crystallography.Biological evaluations of the ferrocene amide derivatives containing pyrimidine-moiety were performed in the K562, U937, MCF-7, A549, Hela, DU145, SGC-7901, HI 975, HL60, MOLT-4 cell lines by using the MTT method. The results showed that the derivatives with electron-donating groups showed almost no antiproliferative activities and the derivatives with electron-withdrawing groups were exhibited better antitumor activity when compared to the positive control TSA and Taxol. Compound 7i showed the best antitumor activity with the mean IC50 value of 5.76 p,mol/L when tested against DU145 cell line and Hela cell line, respectively. In addition, we also test the ferrocene amide derivatives containing pyrazole-moiety against Smmc7721 and SGC7091 by MTT method. The results showed that all the compounds had stronger antiproliferative activities than the positive control 5-Fu. Among them, compound D15 showed the best antitumor activity with the mean IC50 value of 9.8 μg/mL和 10.04 μg/mL against the SGC7091and Smmc7721) respectively.Subsequently SAR studies were performed to determine how the substituents affected the antiproliferative activities.And it provided some information for searching better activity of lead compounds for future.