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Tytuł pozycji:

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.

Tytuł :
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.
Autorzy :
Juvêncio da Silva L; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.; School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.
Dias Barroso FD; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.; School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.
Vieira LS; Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil.
Carlos Mota DR; Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil.
da Silva Firmino BK; Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil.
Rocha da Silva C; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.; School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.
de Farias Cabral VP; School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.
Cândido TM; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.; School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.
Sá LGDAV; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.; School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.
Barbosa da Silva WM; Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil.
Silva J; Department of Chemistry, Group for Theoretical Chemistry and Electrochemistry (GQTE), State University of Ceará, Limoeiro do Norte, Ceará, Brazil.
Marinho ES; Department of Chemistry, Group for Theoretical Chemistry and Electrochemistry (GQTE), State University of Ceará, Limoeiro do Norte, Ceará, Brazil.
Cavalcanti BC; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.
de Moraes MO; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.
Júnior HVN; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.; School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.
de Andrade Neto JB; School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil.
Pokaż więcej
Źródło :
Journal of medical microbiology [J Med Microbiol] 2021 Mar; Vol. 70 (3). Date of Electronic Publication: 2021 Feb 09.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Publication: 2015- : London : Microbiology Society
Original Publication: 1968-1995: Edinburgh, Livingstone.
MeSH Terms :
Antifungal Agents/*pharmacology
Biofilms/*drug effects
Candida/*drug effects
Diazepam/*pharmacology
Drug Resistance, Fungal/*drug effects
Aspartic Acid Endopeptidases/metabolism ; Candida/pathogenicity ; Fluconazole/pharmacology ; Fungal Proteins/metabolism
Contributed Indexing :
Keywords: Biofilms; Candida spp.; Diazepam; Docking; Resistance
Substance Nomenclature :
0 (ALS3 protein, Candida albicans)
0 (Antifungal Agents)
0 (Fungal Proteins)
8VZV102JFY (Fluconazole)
EC 3.4.23.- (Aspartic Acid Endopeptidases)
EC 3.4.23.- (SAP5 protein, Candida albicans)
Q3JTX2Q7TU (Diazepam)
Entry Date(s) :
Date Created: 20210209 Date Completed: 20210408 Latest Revision: 20210408
Update Code :
20210409
DOI :
10.1099/jmm.0.001308
PMID :
33560202
Czasopismo naukowe
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.

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