Gold(I) complexes as antimicrobial agents

Novelli, Federica; Recine, Marco; Sparatore, Fabio; Juliano, Claudia Clelia Assunta

doi:10.1016/s0014-827x(99)00019-1

Cited by 74 publications

(54 citation statements)

References 7 publications

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“…Other inorganic or organic metal compounds, such as lead (Pb) (Lenihan, 1988;Trotter, 1990), tin (Sn) (Barnes & Stoner, 1959;Cooney & Wuertz, 1989), zinc (Zn) (Aarestrup & Hasman, 2004), bismuth (Bi) (Mahony et al, 1999;Ge & Sun, 2007;Yang & Sun, 2007), gold (Au) (Novelli et al, 1999;Ray et al, 2007), cerium (Ce) (Garner & Heppell, 2005), palladium (Pd) (Ray et al, 2007), tellurite (Te) (Taylor, 1999), thallium (Tl) (Kazantzis, 2000) and gallium (Ga) (Chitambar, 2010), have also been investigated or seen limited use as antimicrobials. Of these less heavily used antimicrobial metals, zinc, bismuth and tin are still in common use in consumer products.…”

Section: Metals In Medicine and Agriculture -Past And Present Usesmentioning

confidence: 99%

Bacterial antimicrobial metal ion resistance

Hobman

Crossman

2015

Journal of Medical Microbiology

315

217

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Metals such as mercury, arsenic, copper and silver have been used in various forms as antimicrobials for thousands of years with until recently, little understanding of their mode of action. The discovery of antibiotics and new organic antimicrobial compounds during the twentieth century saw a general decline in the clinical use of antimicrobial metal compounds, with the exception of the rediscovery of the use of silver for burns treatments and niche uses for other metal compounds. Antibiotics and new antimicrobials were regarded as being safer for the patient and more effective than the metal-based compounds they supplanted. Bacterial metal ion resistances were first discovered in the second half of the twentieth century. The detailed mechanisms of resistance have now been characterized in a wide range of bacteria. As the use of antimicrobial metals is limited, it is legitimate to ask: are antimicrobial metal resistances in pathogenic and commensal bacteria important now? This review details the new, rediscovered and 'never went away' uses of antimicrobial metals; examines the prevalence and linkage of antimicrobial metal resistance genes to other antimicrobial resistance genes; and examines the evidence for horizontal transfer of these genes between bacteria. Finally, we discuss the possible implications of the widespread dissemination of these resistances on re-emergent uses of antimicrobial metals and how this could impact upon the antibiotic resistance problem. IntroductionMetals and metalloids have a long empirical history of human usage in medicine and agriculture (as reviewed below), despite problems of host toxicity or doubts about their efficacy. Even now, a few toxic metal(loid) compounds are still first-line drugs or preferred-choice chemotherapeutics or antimicrobials, although the use of most of the previously popular antimicrobial metal(loid)s, such as mercury and arsenic/antimony compounds, has been reduced or phased out in the past 50 or so years. Other metals, such as silver and copper, still have limited uses in agriculture and medicine, but are also increasingly being included in consumer products, from clothing to computer keyboards, and are being promoted as useful additions to our arsenal of antimicrobials. Against this background of their current usage, it is reasonable to ask: what is the relevance of antimicrobial metals and bacterial resistances to them to medical microbiology in the twentyfirst century?Any attempt to address this question must be set against the backdrop of widely known problems and opportunities. We are faced with new and emerging opportunistic nosocomial and community-acquired pathogens; and increasing epidemic and pandemic multidrug-resistant (MDR) pathogens. There is a recognition that the antibiotic discovery pipeline has not delivered significant quantities of new antibiotics in the past few decades, and new formulations and uses for antimicrobial metals as weapons in the antimicrobial armoury are being proposed (Department of Health, 2013;Lemire et al., 2013). ...

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Section: Metals In Medicine and Agriculture -Past And Present Usesmentioning

confidence: 99%

Bacterial antimicrobial metal ion resistance

Hobman

Crossman

2015

Journal of Medical Microbiology

315

217

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“…In this last field, the compounds under investigation include a major collection of the type R 3 PAuL, in which the gold atom is coordinated to a phosphine ligand and L is an O- [26,27], N- [28,29], Cl- [30] or S- [29,[31][32][33][34][35] 2 ], Na 3 [Au(mna) 2 ] (H 2 mna 02-mercaptonicotinic acid) [13] and the cationic complexes [Au(L) 2 ](NO 3 ) 3 (L01-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) [34]. For the latter ligand, compounds of the type [Au(L)]Br, [Au(L)] SCN and [Au(L)]Cl were also prepared [34] and the coexistence of an S-donor ligand and a Cl ligand was also described for [LAuCl] (where L 02,3-diphenyl-1,3,4-thiadiazolium-5-thiolato-S exo ) [36].…”

Section: (L)] [Hq][ag(l)] (Hq0diisopropylammonium)mentioning

confidence: 99%

Synthesis and antimicrobial activities of gold(I) sulfanylcarboxylates

et al. 2012

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Reaction of NaAuCl 4 ·H 2 O and thiodiglycol (1:3 molar ratio) with 3-(aryl)-2-sulfanylpropenoic acids, C NMR spectroscopy. The antimicrobial activities of the complexes against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Pseudomonas aeruginosa and carbapenem-resistant P. aeruginosa were evaluated and compared to those of the equivalent silver(I) complexes. The comparison shows that the gold compounds generally show better activity than the silver analogues against S. aureus and B. subtilis, but low sensitivity against E. coli, P. aeruginosa and C. albicans, suggesting a different mode of antimicrobial action for equivalent silver and gold compounds.

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“…Trx plays an essential role in the synthesis of deoxy-ribose sugars for DNA and in maintenance and perhaps regulation of nuclear redox balance critical to transcription factor activity and gene expression (Arnér and Holmgren, 2000). The increasingly apparent central role of Trx in cellular biochemical processes has made TrxR an attractive target to treat cancer, microbial infections, and inflammatory diseases (Novelli et al, 1999;Becker et al, 2000;Rigobello et al, 2004;Nguyen et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Sublethal concentrations of diverse gold compounds inhibit mammalian cytosolic thioredoxin reductase (TrxR1)

Omata

Folan

Shaw

et al. 2006

Toxicology in Vitro

113

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Thioredoxin reductase (TrxR) reduces thioredoxin (Trx), thereby contributing to cellular redox balance, facilitating the synthesis of deoxy-ribose sugars for DNA synthesis, and regulating redox-sensitive gene expression. Auranofin is a gold compound that potently inhibits TrxR. This inhibition is one suspected mechanism of auranofin's therapeutic benefit in the treatment of rheumatoid arthritis. The use of other gold compounds to treat cancer or inflammatory disease may rely on their ability to inhibit TrxR. In the current study, we tested the hypothesis that a variety of gold compounds may inhibit TrxR.Methods: We exposed rat-TrxR1 to auranofin, gold sodium thiomalate, sodium aurothiosulfate, triphenyl phosphine gold chloride, or gold acetate, and measured TrxR activity ex-vivo. We then compared TrxR1 inhibitory levels of gold compounds to those that inhibited mitochondrial activity of THP1 monocytes and OSC2 epithelial cells, estimated by succinate dedhydrogenase activity.Results: All gold compounds inhibited TrxR1 at concentrations ranging from 5-4000 nM (50% inhibitory concentration). The oxidation state of gold did not correlate with inhibitory potency, but ligand configuration was important. Au(I)-phosphine compounds (triphenyl phosphine gold chloride and auranofin) were the most potent inhibitors of TrxR. All TrxR1 inhibitory concentrations were sublethal to mitochondrial activity in both THP1 and OSC2 cells. AbstractThioredoxin reductase (TrxR) reduces thioredoxin (Trx), thereby contributing to cellular redox balance, facilitating the synthesis of deoxy-ribose sugars for DNA synthesis, and regulating redox-sensitive gene expression. Auranofin is a gold compound that potently inhibits TrxR. This inhibition is one suspected mechanism of auranofin's therapeutic benefit in the treatment of rheumatoid arthritis. The use of other gold compounds to treat cancer or inflammatory disease may rely on their ability to inhibit TrxR. In the current study, we tested the hypothesis that a variety of gold compounds may inhibit TrxR.Methods: We exposed rat-TrxR1 to auranofin, gold sodium thiomalate, sodium aurothiosulfate, triphenyl phosphine gold chloride, or gold acetate, and measured TrxR activity ex-vivo. We then compared TrxR1 inhibitory levels of gold compounds to those that inhibited mitochondrial activity of THP1 monocytes and OSC2 epithelial cells, estimated by succinate dedhydrogenase activity.Results: All gold compounds inhibited TrxR1 at concentrations ranging from 5-4000 nM (50% inhibitory concentration). The oxidation state of gold did not correlate with inhibitory potency, but ligand configuration was important. Au(I)-phosphine compounds (triphenyl phosphine gold chloride and auranofin) were the most potent inhibitors of TrxR. All TrxR1 inhibitory concentrations were sublethal to mitochondrial activity in both THP1 and OSC2 cells.Conclusions: Diverse types of gold compounds may be effective inhibitors of TrxR1 at concentrations that do not suppress cellular mitochondrial function. Inhibition may ...

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Gold(I) complexes as antimicrobial agents

Cited by 74 publications

References 7 publications

Bacterial antimicrobial metal ion resistance

Bacterial antimicrobial metal ion resistance

Synthesis and antimicrobial activities of gold(I) sulfanylcarboxylates

Sublethal concentrations of diverse gold compounds inhibit mammalian cytosolic thioredoxin reductase (TrxR1)

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