Novel bridged heteronuclear Pt(II)-L-Zn(II) complexes with promising antitumor activity

Design of novel heteronuclear platinum(II)-zinc(II) complexes as potential DNA and protein targeting metal-based anticancer agents could be beneficial. The compounds of these two metal ions have different coordination geometry, kinetics properties, affinity, and reactivity towards biologically relevant nucleophiles. According to hard-soft acid base principle, different reactivities of metal centers will result in different coordination modes of biomolecules and in increment of cytotoxicity.

The novel heteronuclear complexes [{cis-PtCl(NH₃)(μ-pyrazine)ZnCl(terpy)}](ClO₄)₂ (Pt-L1-Zn) and [{cis-PtCl(NH₃)(μ-4,4′-bipyridyl)ZnCl(terpy)}](ClO₄)₂ (Pt-L2-Zn) (where terpy = 2,2′:6′,2′′-terpyridine, L1 = pyrazine, L2 = 4,4′-bipyridyl) were synthesized and characterized. The cytotoxic activity of heteronuclear Pt-L1-Zn and Pt-L2-Zn complexes was determined on human colorectal cancer cell line (HCT-116) and human breast cancer cell line (MDA-MB-231). Both complexes significantly reduced cell viability on tested cell lines and exerted significant cytotoxic effects, with better effect on HCT-116 cells than cisplatin, especially after 72 h (IC₅₀ < 0.52 mM). The Pt-L2-Zn complex showed higher activity against human breast cancer cells (MDA-MB-231) than cisplatin after 72 h. The higher reactivity toward DNA constituent and significant cytotoxic activity may be attributed to the different geometries, Lewis acidity of different metal centers, as well as choice of bridging ligands.