N-Picolyl Derivatives of Kemp’s Triamine as Potential Antitumor Agents: A Preliminary Investigation

摘要

Pre-organized tripodal ligands such as the N-picolyl derivatives of cis,cis-1,3,5-triamino-cis,cis-1,3,5-trimethylcyclohexane (>Kemp’s triamine) were prepared as analogs to N,N’,N”- tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (>tachpyr) in hopes of enhancing the rate of formation and stability of the metal complexes. A tricyclic bisaminal was formed via the reduction of the Schiff base while the tri(picolyl) derivative was synthesized via reductive amination of pyridine carboxaldehyde. Their cytotoxicities to the HeLa cell line were evaluated and directly compared to tachpyr and N,N’,N”- tris(2-pyridylmethyl)-tris(2-aminoethyl)amine (>trenpyr). Results indicate that N,N’,N”-tris(2-pyridylmethyl)-cis,cis-1,3,5-triamino-cis,cis-1,3,5-trimethylcyclohexane (>Kemp’s pyr) exhibits cytotoxic activity against the HeLa cancer cell line comparable to tachpyr (IC50 ~ 8.0 µM). Both Kemp’s pyr and tachpyr show higher cytotoxic activity over the aliphatic analogue of trenpyr (IC50 ~ 14 µM) suggesting that the major contributor to the activity is the ligand’s ability to form a stable and tight complex and that the equatorial/axial equilibrium impacting the complex formation for the cyclohexane-based ligands is not significant.