Gold Complexes with N-heterocyclic Carbene Ligands as Antibacterial Agents

点击翻译按钮获取中文摘要

Increasing multidrug resistance is a major concern in the therapy of bacterial infections. Therefore, the development of innovative drugs with new chemical structures and unconventional modes of action is of particular importance. In a pilot project the high efficiency of organometallic gold complexes with N-heterocyclic carbene ligands (gold-NHC-complexes) against several pathogenic bacterial strains was discovered. Especially the high activities against methicillin-resistant S. aureus were of high interest. Moreover, gold-NHC-complexes inhibited the activity of bacterial thioredoxin reductase (TrxR), which is an uncommon mechanism if compared with established types of antibiotics. The project aims at the synthesis and deeper investigation of the potential of gold-NHC-complexes as antibacterial TrxR inhibitors. Moreover, the complexes will be incorporated into known antibiotics and connected with targeting moieties that can be activelytransported into the cells (gold-NHC-conjugates). The new compounds will be subjected to a detailed biological evaluation, which includes antibacterial screening, characterisation of the interaction with TrxR and the identification of alternative modes of drug action. These challenging goals shall be achieved by an interdisciplinary project team consisting of scientists from Technische Universität Braunschweig (Inorganic Medicinal Chemistry) and the Helmholtz Centre for Infection Research (Chemical Biology).