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 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.