Synthesis of 1,3,5-cis,cis-triaminocyclohexane N-pyridyl derivatives as potential antitumor agents

Iron deprivation has been previously proven to be a promising strategy in treating tumor cells. A series of cis,cis-1,3,5-triaminocyclohexane N-pyridyl derivatives as iron-depleting antitumor agents were prepared. Cytotoxic activity of these derivatives was evaluated in the HeLa cancer cell line. Among the tested derivatives, N-ethyl-N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (17) exhibited potent cytotoxicity against this cancer cell line. On the basis of the structure of 17, a bifunctional iron chelator 24 was designed and prepared. Bifunctional agent 24 possessing a maleimide linker that is functional for conjugation to thiolated monoclonal antibodies is a promising lead compound for development of antitumor conjugates for antibody-targeted therapies.