Heterometallic bridged Pt(II)‐Zn(II) complexes: Influence of the substituent in 4′‐position in inert terpy ligand on antigenotoxicity, potential antitumor activity and mechanism of interactions of the complexes with biomolecules

Abstract

The synthesis and characterization of novel hetrometallic complexes [{cis‐PtCl(NH3)2(μ‐4,4′‐bipyridyl)ZnCl(terpy‐Cl)}](ClO4)2 (C1a), [{trans‐PtCl(NH3)2(μ‐4,4′‐bipyridyl)ZnCl(terpy)}](ClO4)2 (C2a), [{cis‐PtCl(NH3)2(μ‐pyrazine)ZnCl(terpy‐Cl)}](ClO4)2 (C3a) and [{trans‐PtCl(NH3)2(μ‐pyrazine)ZnCl(terpy‐Cl)}](ClO4)2 (C4a) (where terpy‐Cl = 4′‐chloro‐2,2′:6′,2′′‐terpyridine) was done. Acid–base titrations were performed by UV–Vis spectrophotometric method to evaluate the pKa values of corresponding aqua complexes. Interactions between complexes and important biomolecules, guanosine‐5′‐monophosphate (5′‐GMP) and glutathione (GSH) were examined by 1H NMR spectroscopy. The chloride substituent at the 4′ position on the middle pyridine ring of terpyridine ligand significantly affects the coordination of biomolecules, as well as overall stability of complexes. The complexes were evaluated in vitro for the antioxidant prevention of DNA damages. All tested novel complexes demonstrated a significant reduction in DNA damage against oxidative modifications of DNA caused by the hydroxyl and peroxyl radicals. Also, cytotoxicity evaluation showed that significant cytotoxicity occurs only after long‐term effect of C1a, C2a and C3a, complexes in HCT‐116 cells. Molecular docking studies predict results in agreement with experimental research.

Modes of Interactions with DNA/HSA Biomolecules and Comparative Cytotoxic Studies of Newly Synthesized Mononuclear Zinc(II) and Heteronuclear Platinum(II)/Zinc(II) Complexes toward Colorectal Cancer Cells

“…The increased cytotoxicity may be attributed to potential interference with multiple intracellular processes and structures that incorporate the zinc(II) ion. The molecular mechanisms governing the response of the colorectal cancer cell line HCT116 to the cytotoxic action of these complexes appear to be complex, involving intricate interplays between various signaling pathways [10][11][12].…”

“…Overview of molecular docking calculations for currently (C1-C5) and previously tested complexes (C1a-C4a and C1b-C2b[11,12]) with DNA. (∆G is binding energy, K i is inhibition constant).…”