Gold(I) complexes with alkylated PTA (1,3,5-triaza-7-phosphaadamantane) phosphanes as anticancer metallodrugs

• Synthesis of gold complexes with water soluble phosphanes.
• Balanced relationship between lipophilicity and hidrophilicity character.
• High cytotoxicity against colon cancer cell lines Caco-2.
• All the complexes induced cell death via apoptotic pathways without appreciable changes in the cell cycle progression.

New stable thiolate gold(I) derivatives containing the alkylated phosphanes [PTA–CH2Ph]Br and [PTA–CH2COOMe]Br derived from 1,3,5-triaza-7-phosphaadamantane (PTA) have been prepared by different routes of synthesis. By the use of basic media to deprotonate the corresponding thiol in the former and by transmetallation reactions from tin (IV) complexes, in the later, thus avoiding side reactions on the phosphane. Strong antiproliferative effects are observed for most of the compounds, including the chloro- and bromo precursors with the series of phosphanes derived from PTA, in human colon cancer cell lines (Caco-2, PD7 and TC7 clones). Apoptosis-induced cell death is found for all compounds, being the thiolate derivatives with [PTA–CH2Ph]Br the most effective, as shown by an annexin-V/propidium iodide double-staining assay.

Gold(I) complexes with PTA related water soluble phosphanes with halogen or thiolate ligands are reported and their anticancer activity have been studied. The best compound is the one in the graphical abstract.Figure optionsDownload as PowerPoint slide