Gold alkynyl complexes with phosphane ligands of the type (alkynyl)Au(I)(phosphane) represent a group of bioorganometallics, which has only recently been evaluated biologically in more detail. Structure-activity-relationship studies regarding the residues of the phosphane ligand (P(Ph)3, P(2-furyl)3, P(DAPTA)3, P(PTA)3, P(Et)3, P(Me)3) of complexes with an 4-ethynylanisole alkyne ligand revealed no strong differences concerning cytotoxicity. However, a relevant preference for the heteroatom free alkyl/aryl residues concerning inhibition of the target enzyme thioredoxin reductase was evident. Complex 1 with the triphenylphosphane ligand was selected for further studies, in which clear effects on cell morphology were monitored by time-lapse microscopy. Effects on cellular signaling were determined by ELISA microarrays and showed a significant induction of the phosphorylation of ERK1 (extracellular signal related kinase 1), ERK2 and HSP27 (heat shock protein 27) in HT-29 cells. Application of 1 in-vivo in a mouse xenograft model was found to be challenging due to the low solubility of the complex and required a formulation strategy based on a peanut oil nanoemulsion.

Departament de Química Inorgànica Universitat de Barcelona Martí i Franquès 1 11 08028 Barcelona Spain

Department of Biology Institut für Pharmazie und Molekulare Biotechnologie Ruperto Carola University of Heidelberg Im Neuenheimer Feld 364 69120 Heidelberg Germany

Gilead Sciences and IOCB Research Center Department of Computational Chemistry Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic 16610 Prague 6 Czech Republic; Department of Physical Chemistry Palacky University 77146 Olomouc Czech Republic

Institute of Medicinal and Pharmaceutical Chemistry Technische Universität Braunschweig Beethovenstrasse 55 38106 Braunschweig Germany; PVZ Center of Pharmaceutical Engineering Franz Liszt Straße 35A 38106 Braunschweig Germany

PVZ Center of Pharmaceutical Engineering Franz Liszt Straße 35A 38106 Braunschweig Germany; Institute of Pharmaceutical Technology Technische Universität Braunschweig Mendelssohnstrasse 1 38106 Braunschweig Germany

State Key Laboratory of Synthetic Chemistry Chemical Biology Center The University of Hong Kong 8 F The Hong Kong Jockey Club Building for Interdisciplinary Research 5 Sassoon Road Pokfulam Hong Kong; Department of Chemistry The University of Hong Kong Pokfulam Road Hong Kong

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