Cellular localization of iron(II) polypyridyl complexes determines their anticancer action mechanisms.

摘要: Elucidation of relationship among cellular uptake, localization and biological activities metal complexes could make great breakthrough in the understanding their action mechanisms provide useful information for rational design metal-based anticancer drugs. Iron(II) have emerged as potential drug candidates with application cancer imaging therapy. Herein, a series iron(II) polypyridyl different lipophilicity were rationally designed, synthesized identified potent agents. The between molecular was also elucidated. results showed that, increase planarity Fe(II) enhanced leading to improved efficacy. hydrophilic complex entered cells through transferring receptor (TfR)-mediated endocytosis, translocated cell nucleus, where they induced S phase cycle arrest triggering DNA damage-mediated p53 pathway. Interestingly, hydrophobic displayed higher efficacy than ones, but shared same uptake pathway (TfR-mediated endocytosis) cells. They accumulated localized cytoplasm, G0/G1 regulation AKT activation downstream effector proteins. These support that regulated by affect mechanisms. Taken together, this study may enhance our on next-generation complexes.