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Novel perspective of anticancer metal-based drugs: Characteristics of heterometallic complexes and their potential applications
1  Department of Natural-Mathematical Sciences, State University of Novi Pazar, Vuka Karadžića bb, 36300 Novi Pazar, Serbia
Academic Editor: Jean Jacques Vanden Eynde

Abstract:

Platinum-based drugs are widely use in medical treatments, but their effectiveness is limited by toxicity. The mechanism of actions is well known, while side effects could be explained by interactions of platinum (soft acid) with biomolecules, which contain sulfur as donor atom (soft bases), such as thiols and the thioethers. One of the possible ways to overcome these limitations could be designing novel heterometallic complexes with metal centers that have different coordination geometry, kinetics properties, affinity, and reactivity towards biological relevant nucleophiles. According to hard-soft acid base principle, dissimilar reactivity of metal centers will result in different coordination modes of biomolecules and in increment of cytotoxicity. The novel heterometallic complexes: [{cis-PtCl(NH3)(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (Pt-L1-Zn), [{cis-PtCl(NH3)(μ-4,4′-bipyridyl)ZnCl(terpy)}](ClO4)2 (Pt-L2-Zn), [{ZnCl(terpy)(μ-pyrazine)CuCl(terpy)}](ClO4)2 (Zn-L1-Cu), [{ZnCl(terpy)(μ-4,4′-bipyridyl)CuCl(terpy)}](ClO4)2 (Zn-L2-Cu) ( terpy = 2,2′:6′,2′′-terpyridine, L1 = pyrazine, L2 = 4,4′-bipyridyl) were synthesized and characterized. The investigation of the interactions between complexes and biomolecules under physiological conditions has pointed out that heterometallic complexes with two different metal centers have great influence on the order of the reactivity and different coordination modes of biomolecules. The investigation of cytotoxic activity has shown that all complexes significantly reduced cell viability on human colorectal cancer cell line (HCT-116) and human breast cancer cell line (MDA-MB-231) lines and exerted significant cytotoxic effects, with better effect on HCT-116 cells than cisplatin, especially after 72 h.

Keywords: zinc(II); platinum(II); copper(II); heterometalic complexes;
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