Applying a Trojan Horse Strategy to Ruthenium Complexes in the Pursuit of Novel Antibacterial Agents

Siderophores are iron chelators secreted by bacteria to scavenge iron(III) from their surrounding environment. They possess their own internalization pathway that is sufficiently unselective to be hijacked, making them suitable for Trojan Horse strategy applications. A commercially available siderophore, deferoxamine B (DFO), was derivatized at the primary amine with carboxylic acids bearing different ligands to afford mono- and bidentate complexes with ruthenium as well as a RAPTA-like complex in which DFO is tethered to the coordinated arene ring. These compounds were tested for antibacterial activity against key ESKAPE pathogens, and antiproliferative studies against healthy (HEK-293) and tumoral (A2780) human cells were performed. Some of the complexes displayed interesting dual anticancer and antibacterial properties. Combining these two properties within a single compound is desirable as patients treated for cancer have a weakened ability for fighting infections.