Nitrate Esters of Heteroaromatic Compounds as Candida albicans CYP51 Enzyme Inhibitors

Four heteroaromatic compounds bearing nitrate esters were selected using a virtual‐screening procedure as putative sterol 14α‐demethylase (CYP51) Candida albicans inhibitors. Compounds were examined for their inhibition on C. albicans growth and biofilm formation as well as for their toxicity. NMR s...

Full description

Saved in:
Bibliographic Details
Published in:ChemMedChem 2018-02, Vol.13 (3), p.251-258
Main Authors: Smiljkovic, Marija, Matsoukas, Minos‐Timotheos, Kritsi, Eftichia, Zelenko, Urska, Grdadolnik, Simona Golic, Calhelha, Ricardo C., Ferreira, Isabel C. F. R., Sankovic‐Babic, Snezana, Glamoclija, Jasmina, Fotopoulou, Theano, Koufaki, Maria, Zoumpoulakis, Panagiotis, Sokovic, Marina
Format: Article
Language:English
Subjects:
14-alpha Demethylase Inhibitors - chemical synthesis
14-alpha Demethylase Inhibitors - pharmacology
14-alpha Demethylase Inhibitors - toxicity
Amides - chemical synthesis
Amides - pharmacology
Amides - toxicity
Animals
Antifungal Agents - chemical synthesis
Antifungal Agents - pharmacology
Antifungal Agents - toxicity
antimicrobial activity
Biofilms
Biofilms - drug effects
Candida albicans
Candida albicans - enzymology
Candidiasis
Cell Line
Cell Survival - drug effects
Cytotoxicity
Drug Design
Enzyme inhibitors
Esters
Esters - chemistry
Esters - pharmacology
Fungi
Hepatocytes
Heterocyclic compounds
Humans
Indoles
Indoles - chemical synthesis
Indoles - pharmacology
Indoles - toxicity
inhibitors
Liver
Liver - cytology
Magnetic resonance spectroscopy
Microbial Sensitivity Tests
Molecular docking
Molecular Docking Simulation
Molecular dynamics
Molecular Dynamics Simulation
Molecular Structure
Nitrate esters
NMR spectroscopy
Protein Binding
Selectivity
Sterol 14-Demethylase - metabolism
Structure-Activity Relationship
Studies
Swine
Toxicity
virtual screening
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Four heteroaromatic compounds bearing nitrate esters were selected using a virtual‐screening procedure as putative sterol 14α‐demethylase (CYP51) Candida albicans inhibitors. Compounds were examined for their inhibition on C. albicans growth and biofilm formation as well as for their toxicity. NMR spectroscopy studies, in silico docking, and molecular dynamics simulations were used to investigate further the selectivity of these compounds to fungal CYP51. All compounds exhibited good antimicrobial properties, indicated with low minimal inhibitory concentrations and ability to inhibit formation of fungal biofilm. Moreover, all of the compounds had the ability to inhibit growth of C. albicans cells. N‐(2‐Nitrooxyethyl)‐1Η‐indole‐2‐carboxamide was the only compound with selectivity on C. albicans CYP51 that did not exhibit cytotoxic effect on cells isolated from liver and should be further investigated for selective application in new leads for the treatment of candidiasis. Stopping growth: Virtual screening reveals some nitrate esters as compounds with antimicrobial activity. From them, N‐(2‐nitrooxyethyl)‐1H‐indol‐2‐carboxamide (MK55) exhibits good inhibitory potential and selectivity on C. albicans growth and no cytotoxic effects.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.201700602