Amides of gold(I) diphosphines prepared from N-heterocyclic sources and their in vitro and in vivo screening for anticancer activity

A series of new neutral mononuclear or dinuclear gold(I) complexes and a cyclic cationic tetranuclear amidogold(I) complex comprising of the phosphines 1,2- bis(dimethylphosphino)ethane (dmpe), μ-1,2–bis(diphenylphosphino)ethane (dppe), μ-1,3- bis(diphenylphosphino)propane (dppp), μ-1,5-bis(diphenylphosphino)pentane (dpppe), μ-1,6- bis(diphenylphosphino)hexane (dpph) or trimethylphosphine, and several N-heterocyclic ring systems (imidazolate, pyrazolate, 1,2,3-triazolate, 1,2,4-triazolate, pyrrolate, 9H-purine-9-ate or 9H-purine-6-amine-9-ate) as ligands, reveal intermolecular aurophilic interactions and 2D channels available for solvent molecules in some of their crystal structures. The antitumour activity of the acyclic gold(I) compounds is highly dependent on the substituents on the phosphorus atoms being highest for phenyl groups and lower for methyl groups. The activity of these compounds against selected cell lines is linked to the length of the carbon bridge between the two phosphorus atoms being highest with a bridge consisting of 5 or 6 carbons. Two compounds with the highest tumour specifities that contain dpppe and pyrazolate (a lipophilic compound) or 1,2,4-triazolate (a hydrophilic compound) induce the apoptic cell death pathway and tolerate a maximum dose of 1.5 μmol/kg when administered to Balb/C mice.Claude Harris Leon Foundation (UEIH), Alexander von Humboldt Stiftung (HGR and SC), NRF (National Research Foundation, South Africa), Harmony Gold Mining Co. Ltd.through Project Autek and the Research Foundation Flanders – FWO (LD)http:// www.sciencedirect.com/science/journal/0162013