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.
Chong
Hyun-soon
HS
Chemistry Section, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. chongjoy@mail.nih.gov
Torti
Frank M
FM
Torti
Suzy V
SV
Brechbiel
Martin W
MW
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003514:Cyclohexylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D018796:Immunoconjugates; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis; D013329:Structure-Activity Relationship
C421444:1,3,5-triaminocyclohexane; D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D018796:Immunoconjugates; D007502:Iron Chelating Agents; D011725:Pyridines; C114047:tachpyr