title: Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents.
abstract: 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 IC50 values, some of them well below those of reference drug fluconazole. The most significant IC50 values were those of 7 against C. glabrata (1.23 μm), C. albicans and C. krusei (both 0.63 μm). 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.
authors.affiliation: Laboratório de Pesquisa em Química Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, Alfenas, MG, 700, Brazil.
authors.forename: Pedro Henrique O
authors.initials: PH
authors.lastname: Abrão
authors.affiliation: Laboratório de Pesquisa em Química Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, Alfenas, MG, 700, Brazil.
authors.forename: Rafael B
authors.initials: RB
authors.lastname: Pizi
authors.affiliation: Laboratório de Pesquisa em Química Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, Alfenas, MG, 700, Brazil.
authors.forename: Thiago B
authors.initials: TB
authors.lastname: de Souza
authors.affiliation: Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700, Alfenas, Brazil.
authors.forename: Naiara C
authors.initials: NC
authors.lastname: Silva
authors.affiliation: Laboratório de Pesquisa em Química Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, Alfenas, MG, 700, Brazil.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Fregnan
authors.affiliation: Laboratório de Pesquisa em Química Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, Alfenas, MG, 700, Brazil.
authors.forename: Fernanda N
authors.initials: FN
authors.lastname: Silva
authors.affiliation: Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700, Alfenas, Brazil.
authors.forename: Luiz Felipe L
authors.initials: LF
authors.lastname: Coelho
authors.affiliation: Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700, Alfenas, Brazil.
authors.forename: Luiz Cosme C
authors.initials: LC
authors.lastname: Malaquias
authors.affiliation: Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700, Alfenas, Brazil.
authors.forename: Amanda Latercia T
authors.initials: AL
authors.lastname: Dias
authors.affiliation: Laboratório de Fitoquímica e Química Medicinal, Instituto de Química, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, Alfenas, MG, 700, Brazil.
authors.forename: Danielle F
authors.initials: DF
authors.lastname: Dias
authors.affiliation: Laboratório de Pesquisa em Química Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, Alfenas, MG, 700, Brazil.
authors.forename: Marcia P
authors.initials: MP
authors.lastname: Veloso
authors.affiliation: Laboratório de Pesquisa em Química Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, Alfenas, MG, 700, Brazil.
authors.forename: Diogo T
authors.initials: DT
authors.lastname: Carvalho
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002175:Candida / Q000254:growth & development*; D002177:Candidiasis / Q000188:drug therapy*; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005054:Eugenol / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D003603:Cytotoxins; D005054:Eugenol
keywords: Candida sp; antifungal action; antimicrobial agents; eugenol; mannich bases