In vitro and in vivo antitumor activities of Ru and Cu complexes with terpyridine derivatives as ligands.

Six terpyridine ligands(L ¹ -L ⁶ ) with chlorophenol or bromophenol moiety were obtained to prepare metal terpyridine derivatives complexes: [Ru(L ¹ )(DMSO)Cl ₂ ] (1), [Ru(L ² )(DMSO)Cl ₂ ] (2), [Ru(L ³ )(DMSO)Cl ₂ ] (3), [Cu(L ⁴ )Br ₂ ]·DMSO (4), Cu(L ⁵ )Br ₂ (5), and [Cu(L ⁶ )Br ₂ ]⋅CH ₃ OH (6). The complexes were fully characterized. Ru complexes 1-3 showed low cytotoxicity against the tested cell lines. Cu complexes 4-6 exhibited higher cytotoxicity against several tested cancer cell lines compared to their ligands and cisplatin, and lower toxicity towards normal human cells. Copper(II) complexes 4-6 arrested T-24 cell cycle in G1 phase. The mechanism studies indicated that complexes 4-6 accumulated in mitochondria of T-24 cells and caused significant reduction of the mitochondrial membrane potential, increase of the intracellular ROS levels and the release of Ca ²⁺ , and the activation of the Caspase cascade, finally inducing apoptosis. Animal studies showed that complex 6 obviously inhibited the tumor growth in a mouse xenograft model bearing T-24 tumor cells without significant toxicity.
Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest for this work.
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