Repurposing of the gold drug auranofin and a review of its derivatives as antibacterial therapeutics

Liu, Yuanhao; Lu, Yunlong; Xu, Zhongren; Ma, Xiaoyan; Chen, Xiuli; Liu, Wukun

doi:10.1016/j.drudis.2022.02.010

Cited by 42 publications

(24 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regard, Auranofin could be a very good candidate for drug repurposing. In fact, this drug was approved for the treatment of rheumatoid arthritis in 1988 and its safety profile is well-known and acceptable; Auranofin is currently under investigation for cancer therapy as a repurposed drug [ 35 ] and has also been proposed to fight a number of bacterial, parasitic and viral infections [ 36 ]. The potential of Auranofin as a drug for the treatment of SARS-CoV-2 recently emerged as a hot topic; a few studies demonstrated its ability to inhibit viral replication by contrasting specific enzymatic activities of the virus [ 5 , 6 , 37 ].…”

Section: Resultsmentioning

confidence: 99%

Gold-Based Metal Drugs as Inhibitors of Coronavirus Proteins: The Inhibition of SARS-CoV-2 Main Protease by Auranofin and Its Analogs

et al. 2022

View full text Add to dashboard Cite

Gold compounds have a long tradition in medicine and offer many opportunities for new therapeutic applications. Herein, we evaluated the lead compound Auranofin and five related gold(I) complexes as possible inhibitors of SARS-CoV-2 Main Protease (SARS-CoV-2 Mpro), a validated drug target for the COVID-19 disease. The investigational panel of gold compounds included Auranofin; three halido analogues, i.e., Au(PEt3)Cl, Au(PEt3)Br, and Au(PEt3)I; and two gold carbene complexes, i.e., Au(NHC)Cl and [Au(NHC)2]PF6. Notably, all these gold compounds, with the only exception of [Au(NHC)2]PF6, turned out to be potent inhibitors of the catalytic activity of SARS-CoV-2 Mpro: the measured Ki values were in the range 2.1–0.4 μM. The reactions of the various gold compounds with SARS-CoV-2 Mpro were subsequently investigated through electrospray ionization (ESI) mass spectrometry (MS) upon a careful optimization of the experimental conditions; the ESI MS spectra provided clear evidence for the formation of tight metallodrug-protein adducts and for the coordination of well defined gold-containing fragments to the SARS-CoV-2 Mpro, again with the only exception of [Au(NHC)2]PF6, The metal-protein stoichiometry was unambiguously determined for the resulting species. The crystal structures of the metallodrug- Mpro adducts were solved in the case of Au(PEt3)Br and Au(NHC)Cl. These crystal structures show that gold coordination occurs at the level of catalytic Cys 145 in the case of Au(NHC)Cl and at the level of both Cys 145 and Cys 156 for Au(PEt3)Br. Tight coordination of gold atoms to functionally relevant cysteine residues is believed to represent the true molecular basis of strong enzyme inhibition.

show abstract

Section: Resultsmentioning

confidence: 99%

Gold-Based Metal Drugs as Inhibitors of Coronavirus Proteins: The Inhibition of SARS-CoV-2 Main Protease by Auranofin and Its Analogs

et al. 2022

View full text Add to dashboard Cite

show abstract

“…CU is commonly used as coloring agent, food additive, and therapeutic drugs in intestinal inflammatory and other diseases 44 . AU was normally used as the anti-cancer and anti-bacteria drugs 45 - 46 . It is reported that CU was shown to improve intestinal barrier function through modulation of intracellular signaling and organization of tight junctions, including reducing IL1-induced activation of p-38 MAPK and subsequently increasing the expression of Myosin Light Chain Kinase involved in the phosphorylation of tight junction proteins and the ensuing disruption of their normal arrangement 47 .…”

Section: Discussionmentioning

confidence: 99%

The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway

Liu¹,

Li²,

Liu³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Our study is to explore the key molecular of Low-density lipoprotein receptor-related protein 6 (LRP6) and the related Wnt/β-catenin pathway regulated by LRP6 during the intestinal barrier dysfunction. Colorectal protein profile analysis showed that LRP6 expression was decreased in dextran sulfate sodium (DSS)-induced colitis mice, and mice received fecal bacteria transplantation from stroke patients. Mice with intestinal hypoxia and intestinal epithelial cells cultured in hypoxia showed decreased expression of LRP6. Overexpression of LPR6 or its N-terminus rescued the Wnt/β-catenin signaling pathway which was inhibited by hypoxia and endoplasmic reticulum stress. In mice overexpressing of LRP6, the expression of β-catenin and DKK1 increased, Bcl2 decreased, and Bax increased. Mice with LRP6 knockout showed an opposite trend, and the expression of Claudin2, Occludin and ZO-1 decreased. Two drugs, curcumin and auranofin could alleviate intestinal barrier damage in DSS-induced colitis mice by targeting LRP-6. Therefore, gut microbiota dysbiosis and hypoxia can inhibit the LRP6 and Wnt/β-catenin pathway, and drugs targeting LRP6 can protect the intestinal barrier.

show abstract

“…Thus, Liu et al discuss recent progress in the exploitation of gold complexes as antibacterial agents. 17 …”

Section: Repurposing Drugs As Anti-infective Therapiesmentioning

confidence: 99%

Drug repurposing: An effective strategy to accelerate contemporary drug discovery

Zhan

Ouyang

2022

Drug Discovery Today

View full text Add to dashboard Cite

Repurposing of the gold drug auranofin and a review of its derivatives as antibacterial therapeutics

Cited by 42 publications

References 91 publications

Gold-Based Metal Drugs as Inhibitors of Coronavirus Proteins: The Inhibition of SARS-CoV-2 Main Protease by Auranofin and Its Analogs

Gold-Based Metal Drugs as Inhibitors of Coronavirus Proteins: The Inhibition of SARS-CoV-2 Main Protease by Auranofin and Its Analogs

The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway

Drug repurposing: An effective strategy to accelerate contemporary drug discovery

Contact Info

Product

Resources

About