Nitrate esters of heteroaromatic compounds as Candida albicans CYP51 enzyme inhibitors

• Autor(a) principal: Smiljković, Marija
• Data de Publicação: 2018
• Outros Autores: Matsoukas, Minos Timotheos, Kritsi, Eftichia, Zelenko, Urska, Grdadolnik, Simona Golic, Calhelha, Ricardo C., Ferreira, Isabel C.F.R., Sankovic-Babic, Snezana, Glamočlija, Jasmina, Fotopoulou, Theano, Koufaki, Maria, Zoumpoulakis, Panagiotis, Soković, Marina
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10198/18554
• topic: Antimicrobial activity; Biofilms; Inhibitors; Nitrate esters; Virtual screening

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.