Antibacterial and antibiofilm activity of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H pyrazoles and thiazoles in multidrug-resistant pathogens.
Ab-MDR
Acinetobacter baumannii
Azoles
KPC
Klebsiella pneumoniae
Journal
Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]
ISSN: 1678-4405
Titre abrégé: Braz J Microbiol
Pays: Brazil
ID NLM: 101095924
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
17
03
2023
accepted:
07
08
2023
pmc-release:
01
09
2024
medline:
4
12
2023
pubmed:
1
9
2023
entrez:
1
9
2023
Statut:
ppublish
Résumé
To find novel antibiotic drugs, six 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H derivatives named 1b, 1d (pyrazoles), 2a, 2b, 2c, and 2d (thiazoles) were evaluated in silico and in vitro. The in silico analyses were based on ADME pharmacokinetic parameters (absorption, distribution, metabolism, and excretion). The in vitro antibacterial activity was evaluated in Gram-positive and Gram-negative species (Staphylococcus aureus ATCC® 25904, Staphylococcus epidermidis ATCC® 35984, Klebsiella pneumoniae ATCC® 700603, and Acinetobacter baumannii ATCC® 19606), by determination of minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), kinetics curve, and antibiofilm assays. As results, the azoles have activity against the Gram-negative species K. pneumoniae ATCC® 700603 and A. baumannii ATCC® 19606. No antibacterial activity was observed for the Gram-positive bacteria evaluated. Thus, the azoles were evaluated against clinical isolates of K. pneumoniae carbapenemase (KPC) and A. baumannii multidrug-resistant (Ab-MDR). All azoles have antibacterial activity against Ab-MDR isolates (Gram-negative) with MIC values between 512 μg/mL and 1,024 μg/mL. Against KPC isolates the azoles 1b, 1d, and 2d present antibacterial activity (MIC = 1,024 μg/mL). In the kinetics curve assay, the 1b and 1d pyrazoles reduced significantly viable cells of Ab-MDR isolates and additionally inhibited 86.6 to 95.8% of the biofilm formation. The in silico results indicate high possibility to permeate the blood-brain barrier (2b) and was predict human gastrointestinal absorption (all evaluated azoles). Considering that the research and development of new antibiotics is a priority for drug-resistant pathogens, our study revealed the antibacterial and antibiofilm activity of novel azoles against K. pneumoniae and A. baumannii pathogens.
Identifiants
pubmed: 37656404
doi: 10.1007/s42770-023-01110-2
pii: 10.1007/s42770-023-01110-2
pmc: PMC10689707
doi:
Substances chimiques
Thiazoles
0
Anti-Bacterial Agents
0
Pyrazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2587-2595Informations de copyright
© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.
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