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Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents
Author(s) -
Abrão Pedro Henrique O.,
Pizi Rafael B.,
Souza Thiago B.,
Silva Naiara C.,
Fregnan Antonio M.,
Silva Fernanda N.,
Coelho Luiz Felipe L.,
Malaquias Luiz Cosme C.,
Dias Amanda Latercia T.,
Dias Danielle F.,
Veloso Marcia P.,
Carvalho Diogo T.
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12504
Subject(s) - eugenol , chemistry , fluconazole , potency , mannich base , broth microdilution , antifungal , in vitro , candida albicans , stereochemistry , pharmacology , biochemistry , organic chemistry , microbiology and biotechnology , minimum inhibitory concentration , biology
New Mannich base‐type eugenol derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 4‐allyl‐2‐methoxy‐6‐(morpholin‐4‐ylmethyl) phenyl benzoate ( 7 ) and 4‐{5‐allyl‐2‐[(4‐chlorobenzoyl)oxy]‐3‐methoxybenzyl}morpholin‐4‐ium chloride ( 8 ) were found to be the most effective antifungal compounds with low IC 50 values, some of them well below those of reference drug fluconazole. The most significant IC 50 values were those of 7 against C. glabrata (1.23 μ m ), C. albicans and C. krusei (both 0.63 μ m ). Additionally, the synthesized compounds were evaluated for their in vitro cytotoxic effects on human mononuclear cells. As result, the cytotoxic activity of eugenol in eukaryotic cells decreased with the introduction of the morpholinyl group. Given these findings, we point out compounds 7 and 8 as the most promising derivatives because they showed potency values greater than those of eugenol and fluconazole and they also presented high selectivity indexes.