New dinuclear gold(III) complex with 1,5-naphthyridine as bridging ligand: synthesis, characterization, DNA/BSA binding studies, and anticancer activity

Gold Bulletin(2024)

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摘要
To elucidate an antitumor drug exhibiting enhanced activity relative to cisplatin, a novel dinuclear gold(III) complex was synthesized, incorporating 1,5-naphthyridine as a bridging ligand. Subsequently, the newly synthesized complex underwent comprehensive characterization using various techniques to validate its structural attributes. The stability of the complex in both water and PBS buffer was assessed through UV–Vis spectroscopy. DNA binding studies were conducted employing UV–Vis, fluorescence spectroscopy, and viscosity measurements. Competitive studies with ethidium bromide (EB) or 4′-hydroxyethidium (HOE) were performed utilizing fluorescence spectroscopy. The findings indicated that the dinuclear gold(III) complex interacts with calf thymus DNA (CT-DNA) through a groove binding mode. Moreover, the investigated complex exhibited significant binding constants for its interaction with human serum albumin (HSA) and bovine serum albumin (BSA) and interactions in the presence of site markers (eosin Y or ibuprofen). The dinuclear gold(III) complex demonstrated notable cytotoxicity against HCT116 and MDA-MB-231 cancer cell lines at 24 and 72 h post-treatment. Furthermore, the complex displayed selectivity by inducing significantly lower cytotoxic activity in healthy cells than in cancerous ones. In support of its antitumor activity, the complex exhibited proapoptotic effects, as evidenced by increased caspase 9 activity and low percentages of necrosis. Molecular docking simulations were employed to corroborate all experimentally obtained results.
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关键词
Gold(III),1,5-Naphthyridine,DNA/BSA binding studies,Cytotoxicity activity,Apoptosis via caspases
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