S-Propargylthiopyridine Phosphane Derivatives As Anticancer Agents: Characterization and Antitumor Activity

Abstract

S-Propargylthiopyridine phosphane gold(I) derivatives with the water-soluble phosphanes PTA (1,3,5-triaza-7-phosphaadamantane), DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane), and TPPTS (sodium triphenylphosphane trisulfonate) are described and used as metalloligands by coordination to copper(I). New heteronuclear gold(I) and copper(I) complexes of the type [Au2Cu(C≡CCH2SC5H4N)2L2] (L = PTA, DAPTA, PPh3, TPPTS) and [AuCu(C≡CCH2SC5H4N)(L)(PPh3)2]NO3 (L = PTA, DAPTA) are reported. The X-ray crystal structure of [Au(C≡CCH2SC5H4N)(PTA)] (1), which confirms the coordination of the metallic center to the alkyne unit, displays a zigzag polymeric chain with short gold–gold contacts of 3.2680(16) Å. Strong antiproliferative effects are found for most of the new complexes in human colon cancer cell lines (Caco-2, PD7, and TC7 clones), with these effects being more pronounced than for the reference drugs cisplatin and auranofin, especially for the heterodimetallic derivatives, which are markedly more active than the corresponding mononuclear precursors. Apoptosis-induced cell death is found for all compounds, as shown by an annexin-V/propidium iodide double-staining assay.