Advisor(s)
Abstract(s)
Four heteroaromatic compounds bearing nitrate esters were
selected using a virtual-screening procedure as putative sterol
14a-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)-1Hindole-
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.
Description
Keywords
Antimicrobial activity Biofilms Inhibitors Nitrate esters Virtual screening
Pedagogical Context
Citation
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 (2018). Nitrate Esters of Heteroaromatic Compounds as Candida albicans CYP51 Enzyme Inhibitors. ChemMedChem. ISSN 1860-7179. 13, p. 251-258