Department of Molecular Microbiology, Groningen Institute for Biomolecular Sciences and Biotechnology, University of Groningen, 9747 AG, Groningen, The Netherlands.
Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, 9713AV, Groningen, The Netherlands.
ChemMedChem. 2021 Oct 6;16(19):3060-3070. doi: 10.1002/cmdc.202100342. Epub 2021 Jul 23.
The rise of antimicrobial resistance has necessitated novel strategies to efficiently combat pathogenic bacteria. Metal-based compounds have been proven as a possible alternative to classical organic drugs. Here, we have assessed the antibacterial activity of seven gold complexes of different families. One compound, a cyclometalated Au(III) C^N complex, showed activity against Gram-positive bacteria, including multi-drug resistant clinical strains. The mechanism of action of this compound was studied in Bacillus subtilis. Overall, the studies point towards a complex mode of antibacterial action, which does not include induction of oxidative stress or cell membrane damage. A number of genes related to metal transport and homeostasis were upregulated upon short treatment of the cells with gold compound. Toxicity tests conducted on precision-cut mouse tissue slices ex vivo revealed that the organogold compound is poorly toxic to mouse liver and kidney tissues, and may thus, be treated as an antibacterial drug candidate.
抗菌药物耐药性的出现，需要新的策略来有效对抗致病菌。金属基化合物已被证明是一种替代传统有机药物的可能选择。在这里，我们评估了七种不同家族的金配合物的抗菌活性。一种化合物，一种环金属化的 Au(III)C^N 配合物，对革兰氏阳性菌表现出活性，包括多药耐药的临床菌株。该化合物的作用机制在枯草芽孢杆菌中进行了研究。总的来说，研究表明该化合物的抗菌作用方式复杂，不包括诱导氧化应激或细胞膜损伤。用金化合物短时间处理细胞后，许多与金属转运和稳态相关的基因被上调。在离体的小鼠组织切片上进行的毒性试验表明，该有机金化合物对小鼠的肝和肾组织毒性较低，因此可能被视为一种候选抗菌药物。
