Repurposing of Auranofin Against Bacterial Infections: An In silico and In vitro Study

Sharma, Nidhi; Singh, Arti; Sharma, Ruchika; Kumar, Anoop

doi:10.2174/1386207323666200717155640

Cited by 12 publications

(9 citation statements)

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“…Combining old drugs with front-line medication is common, but such studies are still limited regarding ARF and HOK. Additive interactions, but rarely synergistic, were reported when combining ARF with antibiotics against pathogenic bacteria [20,21,68,69]. Similar findings were reported when combining ARF with fluconazole or amphotericin B against pathogenic yeasts [23,25], which is consistent with the few additive interactions observed for the combination of ARF with VRC.…”

Section: Discussionsupporting

confidence: 80%

“…Auranofin inhibits the HMW-TrxR via irreversible binding to its selenocysteinyl residue [16], but its inhibitory activity was also reported against LMW-TrxR lacking selenocysteine [17,18]. Therefore, it has been proposed for many infectious diseases, including bacterial, parasitic, and fungal infections [19][20][21][22][23][24]. In fungi, ARF demonstrated promising in vitro activity against several Candida species or Cryptococcus (Cr.)…”

Section: Introductionmentioning

confidence: 99%

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Repurposing of auranofin and honokiol as antifungals against Scedosporium species and the related fungus Lomentospora prolificans

et al. 2021

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The slowing-down de novo drug-discovery emphasized the importance of repurposing old drugs. This is particularly true when combating infections caused by therapy-refractory microorganisms, such as Scedosporium species and Lomentospora prolificans. Recent studies on Scedosporium responses to oxidative stress underscored the importance of targeting the underlying mechanisms. Auranofin, ebselen, PX-12, honokiol, and to a lesser extent, conoidin A are known to disturb redox-homeostasis systems in many organisms. Their antifungal activity was assessed against 27 isolates belonging to the major Scedosporium species: S. apiospermum, S. aurantiacum, S. boydii, S. dehoogii, S. minutisporum, and Lomentospora prolificans. Auranofin and honokiol were the most active against all Scedosporium species (mean MIC 50 values of 2.875 and 6.143 μg/ml, respectively) and against L. prolificans isolates (mean MIC 50 values of 4.0 and 3.563μg/ml respectively). Combinations of auranofin with voriconazole or honokiol revealed additive effects against 9/27 and 18/27 isolates, respectively. Synergistic interaction between auranofin and honokiol was only found against one isolate of L. prolificans. The effects of auranofin upon exposure to oxidative stress were also investigated. For all species except S. dehoogii, the maximal growth in the presence of auranofin significantly decreased when adding a sublethal dose of menadione. The analysis of the expression of genes encoding oxidoreductase enzymes upon exposure of S. apiospermum to honokiol unveiled the upregulation of many genes, especially those coding peroxiredoxins, thioredoxin reductases, and glutaredoxins. Altogether, these data suggest that auranofin and honokiol act via dampening the redox balance and support their repurposing as antifungals against Scedosporium species and L. prolificans.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Repurposing of auranofin and honokiol as antifungals against Scedosporium species and the related fungus Lomentospora prolificans

et al. 2021

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“…Solutions were added according to the experimental grouping of 96‐well microtiter plate as shown above. The absorbance of samples was recorded using a microplate reader at OD 625nm for a period of 48 h 8,20 …”

Section: Methodsmentioning

confidence: 99%

“…The antibacterial potential of selected phytomolecules was determined in terms of the percent retardation of growth using the equation, R (%) = [( C 48 –C 0 ) ‐ ( T 48 ‐T 0 )] × 100 / ( C 48 ‐C 0 ). The absorbance of samples was taken at 625 nm 8 …”

Section: Methodsmentioning

confidence: 99%

“…Tackling the mechanisms of antibiotic resistance and looking for new antibacterial agents, one can explore the alternate use of already approved drugs (drug repurposing). It reduces the cost and time that is involved in drug discovery and the development of new chemical entities (NCEs) 7,8 . Currently, various advanced computational techniques are being used for screening a large number of compounds to get the most promising one in terms of safety and efficacy 9 .…”

Section: Introductionmentioning

confidence: 99%

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Antibacterial potential of selected phytomolecules: An experimental study

Jhanji

Singh

Kumar

2021

Microbiology and Immunology

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Antibiotic resistance is a snowballing international threat. Some of the antibiotics have lost their effectiveness due to overuse and underuse. Thus, there is an urgent need to tackle this global challenge, either by inhibiting the resistance mechanisms or by the development of new chemical entities. Thus, in the current study, the antibacterial activity of selected phytomolecules was investigated against bacterial strains, alone and in combination, with standard drugs. The antibacterial potential of these phytomolecules was explored using in vitro assays (microtiter assay, bacterial growth kinetics, percentage retardation of growth, and antimicrobial synergy study) and in vivo studies (zebrafish infection model). In vitro and in vivo studies have shown promising antibacterial effects against, both, Gram‐positive and Gram‐negative bacteria. Moreover, a cell viability assay also indicated the cytoprotective effect of these phytomolecules in combination with standard antibiotics (SABX). Thus, these phytomolecules could be a promising broad‐spectrum antibacterial agent in combination with standard antibiotics.

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Neuroprotective potentials of ferulic acid against intracerebral hemorrhage COVID-19 through using network pharmacology approach and molecular docking analysis

Dong,

Tan,

Tang

et al. 2023

Current Research in Toxicology

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Repurposing of Auranofin Against Bacterial Infections: An In silico and In vitro Study

Cited by 12 publications

References 0 publications

Repurposing of auranofin and honokiol as antifungals against Scedosporium species and the related fungus Lomentospora prolificans

Repurposing of auranofin and honokiol as antifungals against Scedosporium species and the related fungus Lomentospora prolificans

Antibacterial potential of selected phytomolecules: An experimental study

Neuroprotective potentials of ferulic acid against intracerebral hemorrhage COVID-19 through using network pharmacology approach and molecular docking analysis

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