Synergistic Effects of Ketamine and Azole Derivatives on<i>Candida</i>Spp. Resistance to Fluconazole

Neto, João Batista de Andrade; Silva, Cecília Rocha da; Barroso, Fátima Daiana Dias; Sá, Lívia Gurgel do Amaral Valente; Campos, Rosana de Sousa; Nascimento, Francisca Bruna Stefany Aires do; Sampaio, Letícia Serpa; Silva, Anderson Ramos da; Silva, Lisandra Juvêncio da; Carneiro, Igor de Sá; Queiroz, Helaine A; Mesquita, Jacó Ricarte Lima de; Cavalcanti, Bruno C.; Moraes, Manoel Odoríco de; Júnior, Hélio Vitoriano Nobre

doi:10.2217/fmb-2019-0082

Cited by 18 publications

(13 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The activity of etomidate against S. aureus, E. coli, P. aeruginosa, A. baumannii and E. coli ESBL [13] has already been cited in the literature, but its activity against growing biofilms has not yet been reported. The activity of the anaesthetics ketamine and etomidate has recently been demonstrated against clinical fluconazole-resistant Candida isolates in planktonic and biofilm form [12,14]. Another important factor demonstrated in our results was the reduction of C. albicans cell wall mannoproteins caused by treatment with etomidate.…”

Section: Discussionsupporting

confidence: 58%

“…Some studies have reported the therapeutic repurposing of anaesthetic drugs. These papers have described the antimicrobial activity of drugs such as propofol, midazolam, ketamine and etomidate against different micro-organisms [12][13][14]. These authors have reported antimicrobial effects against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus hominis, Streptococcus epidermidis, Streptococcus pyogenes, Klebsiella pneumoniae, Acinetobacter baumannii and C. albicans.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

Sá

Silva

Neto

et al. 2020

Journal of Medical Microbiology

Self Cite

View full text Add to dashboard Cite

This study evaluated the effect of etomidate against biofilms of Candida spp. and analysed through molecular docking the interaction of this drug with ALS3, an important protein for fungal adhesion. Three fluconazole-resistant fungi were used: Candida albicans, Candida parapsilosis and Candida tropicalis. Growing biofilms were exposed to etomidate at 31.25–500 µg ml−1. Then, an ALS3 adhesive protein from C. albicans was analysed through a molecular mapping technique, composed of a sequence of algorithms to perform molecular mapping simulation based on classic force field theory. Etomidate showed antifungal activity against growing biofilms of resistant C. albicans, C. parapsilosis and C. tropicalis at all concentrations used in the study. The etomidate coupling analysis revealed three interactions with the residues of interest compared to hepta-threonine, which remained at the ALS3 site. In addition, etomidate decreased the expression of mannoproteins on the surface of C. albicans. These results revealed that etomidate inhibited the growth of biofilms.

show abstract

Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

Sá

Silva

Neto

et al. 2020

Journal of Medical Microbiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) method was used to determine DNA fragmentation according to Andrade [25, 26]. The samples were treated with 7 % paraformaldehyde and then with 1 % Triton X-100 for 10 min.…”

Section: Methodsmentioning

confidence: 99%

“…Intracellular sterases hydrolyze CM-H2DCFDA to a non-fluorescent compound (NFC), which is rapidly oxidized to NFDC (2.7=-dichlorofluorescein), a compound that produces high fluorescence. The fluorescence intensity of DCF is proportional to the production of ROS [25,26].…”

Section: Assessment Of the Production Of Reactive Oxygen Species (Ros)mentioning

confidence: 99%

Diazepam’s antifungal activity in fluconazole-resistant Candida spp. and biofilm inhibition in C. albicans: evaluation of the relationship with the proteins ALS3 and SAP5

Silva

Barroso

Vieira

et al. 2021

Journal of Medical Microbiology

Self Cite

View full text Add to dashboard Cite

The genus Candida spp. has been highlighted as one of the main etiological agents causing fungal infections, with Candida albicans being the most prominent, responsible for most cases of candidemia. Due to its capacity for invasion and tissue adhesion, it is associated with the formation of biofilms, mainly in the environment and hospital devices, decreasing the effectiveness of available treatments. The repositioning of drugs, which is characterized by the use of drugs already on the market for other purposes, together with molecular-docking methods can be used aiming at the faster development of new antifungals to combat micro-organisms. This study aimed to evaluate the antifungal effect of diazepam on mature C. albicans biofilms in vitro and its action on biofilm in formation, as well as its mechanism of action and interaction with structures related to the adhesion of C. albicans, ALS3 and SAP5. To determine the MIC, the broth microdilution test was used according to protocol M27-A3 (CLSI, 2008). In vitro biofilm formation tests were performed using 96-well plates, followed by molecular-docking protocols to analyse the binding agent interaction with ALS3 and SAP5 targets. The results indicate that diazepam has antimicrobial activity against planktonic cells of Candida spp. and C. albicans biofilms, interacting with important virulence factors related to biofilm formation (ALS3 and SAP5). In addition, treatment with diazepam triggered a series of events in C. albicans cells, such as loss of membrane integrity, mitochondrial depolarization and increased production of EROs, causing DNA damage and consequent cell apoptosis.

show abstract

“…Incl. E. dermatitidis [205] ketamine [206] ibuprofen [207] chlorhexidine Incl. C. auris [208] ganetespib [209]…”

Section: D-penicillamineunclassified

Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing

2022

View full text Add to dashboard Cite

show abstract

Synergistic Effects of Ketamine and Azole Derivatives onCandidaSpp. Resistance to Fluconazole

Cited by 18 publications

References 51 publications

Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

Diazepam’s antifungal activity in fluconazole-resistant Candida spp. and biofilm inhibition in C. albicans: evaluation of the relationship with the proteins ALS3 and SAP5

Advances in Antifungal Development: Discovery of New Drugs and Drug Repurposing

Contact Info

Product

Resources

About