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Nitrate Esters of Heteroaromatic Compounds as Candida albicans CYP51 Enzyme Inhibitors
Author(s) -
Smiljkovic Marija,
Matsoukas MinosTimotheos,
Kritsi Eftichia,
Zelenko Urska,
Grdadolnik Simona Golic,
Calhelha Ricardo C.,
Ferreira Isabel C. F. R.,
SankovicBabic Snezana,
Glamoclija Jasmina,
Fotopoulou Theano,
Koufaki Maria,
Zoumpoulakis Panagiotis,
Sokovic Marina
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700602
Subject(s) - candida albicans , biofilm , corpus albicans , chemistry , docking (animal) , indole test , selectivity , stereochemistry , antimicrobial , biochemistry , microbiology and biotechnology , bacteria , biology , organic chemistry , medicine , genetics , nursing , catalysis
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)‐1 Η ‐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.