Synthesis of CpM(CO)3–DAB and –PAMAM Dendrimer Conjugates and Preliminary Evaluation of Their Biological Activity

Abstract

AbstractDendrimers of different generations and core structures [diaminobutane poly(propylenimine) (DAB) G1, G2, G3; poly(amidoamine) (PAMAM) G1] were chosen as carriers for bioactive organometallic half‐sandwich complexes of the type CpM(CO)3 (Cp = cyclopentadienyl, M = Mn or Re) to study the influence of these parameters on their biological activity against cancer cells. Structure–activity relationships were determined by variation of the metal center as well as the type, molecular weight, and number of terminal functional groups of the dendrimer conjugates. All conjugates were characterized by IR and NMR spectroscopy as well as HPLC. Their biological activity was determined on MCF‐7 human breast cancer cells by the resazurin assay. Interestingly, the most‐active compounds were the first‐generation dendrimer conjugates. The Mn and Re series showed nearly the same activities. Thus, the cytotoxicity of the dendrimer conjugates does not seem to directly correlate with the type or number of terminal functional groups. Rather, it points to a mechanism of action that is different from that previously observed for peptide conjugates with similar CpM(CO)3 functional groups.