Author(s): Santos, Marcelo Henrique dos ; Hipólito, Taciane Maíra Magalhães ; Bastos, Guilherme Tadeu Lemos ; Barbosa, Thúlio Wliandon Lemos ; Souza, Thiago Belarmino de ; Coelho, Luiz Felipe Leomil ; Dias, Amanda Latércia Tranches ; Rodríguez, Ihosvany Camps ; Dias, Danielle Ferreira ; Franco, Lucas Lopardi ; Carvalho, Diogo Teixeira
Date: 2018
Origin: Oasisbr
Subject(s): Eugenol; Glucosides; Antifungals; Candida spp; Molecular docking
Seventeen new synthetic derivatives of eugenol (6, 8–15 and 8′‐15′) were planned following literature reports on antifungal activities of nitroeugenol and eugenol glucoside. The anti‐Candida activity of these compounds was investigated by in vitro assay and the cytotoxicity evaluation was performed with the most active compounds. The peracetylated glucosides presented better biological results than their hydroxylated analogues. The glucoside 11, a 4‐nitrobenzamide, showed the best potency (MIC50 range 11.0‐151.84 μM), the wider spectrum of action and overall the best selectivity indexes, especially against C. tropicalis (~30) and C. krusei (~15). In order to investigate its possible mechanism of action, glucoside 11 was subjected to molecular docking studies with Candida sp. enzymes involved in ergosterol biosynthesis. Results have shown that the peracetyl glucosyl moiety and the 4‐nitrobenzamide group in 11 are effectively involved in its high affinity with the active site of squalene epoxidase.
