Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Via Giuseppe Fanin 40, I-40127 Bologna, Italy.
Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, I-50019 Sesto Fiorentino, Italy.
Dalton Trans. 2021 Oct 19;50(40):14444-14452. doi: 10.1039/d1dt02488d.
A few gold compounds were recently found to show antimicrobial properties , holding great promise for the discovery of new drugs to overcome antibiotic resistance. Here, the inhibition of the bacterial virulence factor urease by four Au(I)-compounds, namely Au(PEt)Cl, Au(PEt)Br, Au(PEt)I and [Au(PEt)]Cl, obtained from the antiarthritic Au(I)-drug Auranofin and earlier reported to act as antimicrobials, is investigated. The three monophosphino Au(I) complexes showed IC values in the 30-100 nM range, while the diphosphino Au(I) complex, though being less active, still showed a IC value of 7 μM. The structural basis for this inhibition was provided by solving the crystal structures of urease co-crystallized with Au(PEt)I and [Au(PEt)]Cl: at least two Au(I) ions bind the enzyme in a flap domain involved in the catalysis, thus obliterating enzyme activity. Peculiar changes observed in the two structures reveal implications for the mechanism of soft metal binding and enzyme inactivation.
最近发现一些金化合物具有抗菌特性，为发现克服抗生素耐药性的新药提供了很大的希望。在这里，研究了四种 Au(I)-化合物（即 Au(PEt)Cl、Au(PEt)Br、Au(PEt)I 和 [Au(PEt)]Cl）对细菌毒力因子脲酶的抑制作用，这些化合物来自抗关节炎的 Au(I)-药物金诺芬，并且之前报道具有抗菌作用。三种单膦 Au(I)配合物的 IC 值在 30-100 nM 范围内，而二膦 Au(I)配合物虽然活性较低，但仍显示出 7 μM 的 IC 值。这种抑制的结构基础是通过解析与 Au(PEt)I 和 [Au(PEt)]Cl 共结晶的脲酶的晶体结构提供的：至少两个 Au(I)离子结合在参与催化的 flap 结构域中的酶上，从而破坏酶的活性。在这两个结构中观察到的特殊变化揭示了软金属结合和酶失活机制的影响。
