New potent antifungal triazole alcohols containing N-benzylpiperazine carbodithioate moiety: Synthesis, in vitro evaluation and in silico study.
1H-1,2,4-triazole
Antifungal activity
Azole antifungals
Lanosterol 14α-demethylase
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
16
11
2018
revised:
26
05
2019
accepted:
07
06
2019
pubmed:
24
6
2019
medline:
21
10
2020
entrez:
24
6
2019
Statut:
ppublish
Résumé
A number of 1H-1,2,4-triazole alcohols containing N-(halobenzyl)piperazine carbodithioate moiety have been designed and synthesized as potent antifungal agents. In vitro bioassays against different Candida species including C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis revealed that the N-(4-chlorobenzyl) derivative (6b) with MIC values of 0.063-0.5 µg/mL had the best profile of activity, being 4-32 times more potent than fluconazole. Docking simulation studies confirmed the better fitting of compound 6b in the active site of lanosterol 14α-demethylase (CYP51) enzyme, the main target of azole antifungals. Particularly, the potential of compound 6b against fluconazole-resistant isolates along with its minimal toxicity against human erythrocytes and HepG2 cells make this prototype compound as a good lead for discovery of potent and safe antifungal agents.
Identifiants
pubmed: 31229796
pii: S0045-2068(18)31331-2
doi: 10.1016/j.bioorg.2019.103060
pii:
doi:
Substances chimiques
Alcohols
0
Antifungal Agents
0
N-benzylpiperazine
0
Piperazines
0
Triazoles
0
Types de publication
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103060Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.