New Cyclams and Their Copper(II) and Iron(III) Complexes: Synthesis and Potential Application as Anticancer Agents

Abstract

New cyclam derivatives (HOCH₂ CH₂ CH₂ )₂ (PhCH₂ )₂ Cyclam and (HOCH₂ CH₂ CH₂ )₂ ( ${4\text{-}\mathrm{CF}{3}_{}}^{}$ PhCH₂ )₂ Cyclam, as well as their Cu^II and Fe^III complexes, were synthesized and characterized and their stability in cellular media was assessed. The cytotoxic effect of all compounds was examined on human cervical cancer (HeLa) cells, revealing strong anticancer activity. After 24 h, only complexes with the (HOCH₂ CH₂ CH₂ )₂ ( ${4\text{-}\mathrm{CF}{3}_{}}^{}$ PhCH₂ )₂ Cyclam ligand are cytotoxic, whereas after incubation for 72 h all compounds show significant antiproliferative effects. Notably, compounds containing ${4\text{-}\mathrm{CF}{3}_{}}^{}$ PhCH₂ pendant arms on the cyclam ring revealed the most activity, with cytotoxicity values up to 12 times higher than those of cisplatin. All metal complexes seem to induce cell death through the formation of reactive oxygen species.

Keywords: cancer; cyclams; cytotoxicity; macrocycles; metallodrugs.