Antifungal Activity of New Eugenol-Benzoxazole Hybrids against Candida

Eugenol is a natural allylphenol responsible for a wide range of biological activities, especially antimicrobial. Benzoxazoles are heterocycles with recognized antimicrobial activities. This paper describes the design, synthesis, and the biological results for benzoxazole type derivatives of eugenol as antifungal agents. The products were obtained in good yields by a four-step synthetic sequence involving aromatic nitration, nitroreduction, amide formation, and cycle condensation. They were evaluated against species of Candida spp. in microdilution assays, and four products (5a, 5b′, 5c, and 5d′) were about five times more active than eugenol against C. albicans and C. glabrata. Two of them (5b′ and 5d′) showed good activity against C. krusei, a species which is naturally resistant to fluconazole. Furthermore, the active products were more selective than eugenol against human blood cells, showing that they are interesting substances for further optimization

Antifungal Activity of New Eugenol-Benzoxazole Hybrids against Candida spp.

Eugenol is a natural allylphenol responsible for a wide range of biological activities, especially antimicrobial. Benzoxazoles are heterocycles with recognized antimicrobial activities. This paper describes the design, synthesis, and the biological results for benzoxazole type derivatives of eugenol as antifungal agents. The products were obtained in good yields by a four-step synthetic sequence involving aromatic nitration, nitroreduction, amide formation, and cycle condensation. They were evaluated against species of Candida spp. in microdilution assays, and four products (5a, 5b′, 5c, and 5d′) were about five times more active than eugenol against C. albicans and C. glabrata. Two of them (5b′ and 5d′) showed good activity against C. krusei, a species which is naturally resistant to fluconazole. Furthermore, the active products were more selective than eugenol against human blood cells, showing that they are interesting substances for further optimization

Synthesis, activity, and docking studies of eugenol‐based glucosides as new agents against Candida

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

Synthesis, activity and docking studies of eugenol-based glucosides as new agents against Candida sp.

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