Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents

Pedro Henrique O. Abrão; Rafael B. Pizi; Thiago B. de Souza; Naiara C. Silva; Antonio M. Fregnan; Fernanda N. Silva; Luiz Felipe L. Coelho; Luiz Cosme C. Malaquias; Amanda Latercia T. Dias; Danielle F. Dias; Marcia P. Veloso; Diogo T. Carvalho

doi:10.1111/cbdd.12504

journal article Feb 19, 2015

Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents

Pedro Henrique O. Abrão Rafael B. Pizi Thiago B. de Souza Naiara C. Silva Antonio M. Fregnan Fernanda N. Silva Luiz Felipe L. Coelho Luiz Cosme C. Malaquias Amanda Latercia T. Dias Danielle F. Dias Marcia P. Veloso Diogo T. Carvalho

Chemical Biology & Drug Design Vol. 86 No. 4 pp. 459-465 · Wiley

View at Publisher Save 10.1111/cbdd.12504

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.

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Details

Published: Feb 19, 2015
Vol/Issue: 86(4)
Pages: 459-465
License: View

Authors

P

Pedro Henrique O. Abrão

Laboratório de Pesquisa em Química Farmacêutica Faculdade de Ciências Farmacêuticas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva Alfenas MG 700 Brazil

R

Rafael B. Pizi

Laboratório de Pesquisa em Química Farmacêutica Faculdade de Ciências Farmacêuticas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva Alfenas MG 700 Brazil

T

Thiago B. de Souza

Laboratório de Pesquisa em Química Farmacêutica Faculdade de Ciências Farmacêuticas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva Alfenas MG 700 Brazil

N

Naiara C. Silva

Departamento de Microbiologia e Imunologia Instituto de Ciências Biomédicas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva 700 Alfenas Brazil

A

Antonio M. Fregnan

Laboratório de Pesquisa em Química Farmacêutica Faculdade de Ciências Farmacêuticas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva Alfenas MG 700 Brazil

F

Fernanda N. Silva

Laboratório de Pesquisa em Química Farmacêutica Faculdade de Ciências Farmacêuticas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva Alfenas MG 700 Brazil

L

Luiz Felipe L. Coelho

Departamento de Microbiologia e Imunologia Instituto de Ciências Biomédicas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva 700 Alfenas Brazil

L

Luiz Cosme C. Malaquias

Departamento de Microbiologia e Imunologia Instituto de Ciências Biomédicas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva 700 Alfenas Brazil

A

Amanda Latercia T. Dias

Departamento de Microbiologia e Imunologia Instituto de Ciências Biomédicas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva 700 Alfenas Brazil

D

Danielle F. Dias

Laboratório de Fitoquímica e Química Medicinal Instituto de Química Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva Alfenas MG 700 Brazil

M

Marcia P. Veloso

Laboratório de Pesquisa em Química Farmacêutica Faculdade de Ciências Farmacêuticas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva Alfenas MG 700 Brazil

D

Diogo T. Carvalho

Laboratório de Pesquisa em Química Farmacêutica Faculdade de Ciências Farmacêuticas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva Alfenas MG 700 Brazil

Funding

FAPEMIG, Brazil Award: APQ-01641-12

Cite This Article

Pedro Henrique O. Abrão, Rafael B. Pizi, Thiago B. de Souza, et al. (2015). Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents. Chemical Biology & Drug Design, 86(4), 459-465. https://doi.org/10.1111/cbdd.12504

Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents

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