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.
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Abrão et al. found that two Mannich base-type eugenol derivatives were the most effective, particularly against C. glabrata, C. albicans, and C. krusei, with IC50 values below those of fluconazole.
“Abrão et al. [267] evaluated the anti-candidal activity of new Mannich base-type eugenol derivatives and found that 4-allyl-2-methoxy-6-(morpholin-4-ylmethyl) phenyl benzoate and 4-{5-allyl-2[(4-chlorobenzoyl)oxy]-3-methoxybenzyl}morpholin-4-ium chloride were the most effective, particularly against C. glabrata, C. albicans, and C. krusei, with IC50 values below those of fluconazole.”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [267]
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Candida glabrata Biofilms: How Far Have We Come?
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- Authors
- Abrão, P. H. O., Pizi, R. B., de Souza, T. B., Silva, N. C., Fregnan, A. M., Silva, F. N., Coelho, L. F. L., Malaquias, L. C. C., Dias, A. L. T., Dias, D. F., Veloso, M. P., & Carvalho, D. T.
- Affiliations
- Universidade Federal de Alfenas (BR)
- Laboratório de Pesquisa em Química Farmacêutica Faculdade de Ciências Farmacêuticas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva Alfenas MG 700 Brazil
- Departamento de Microbiologia e Imunologia Instituto de Ciências Biomédicas Universidade Federal de Alfenas Rua Gabriel Monteiro da Silva 700 Alfenas Brazil
- Corresponding author
- Carvalho, Diogo T.
- Venue
- Chemical Biology & Drug Design
- Publisher
- Wiley
- Published
- 2015-02-19
- Volume
- 86
- Issue
- 4
- Pages
- 459-465
- ISSN
- 1747-0277 (ISSN-L)
- 1747-0285
- OpenAlex
- W2053034414
- Cited by
- 45
- References
- 39
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 3
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chemical Biology & Drug Design (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fapemig, Brazil (APQ-01641-12)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and Biological Evaluation
- Keywords
- eugenol derivatives, Mannich bases, antifungal agents, Candida albicans, Candida glabrata, Candida krusei, morpholine, cytotoxicity, mononuclear cells, selectivity index, fluconazole comparison, antifungal activity
- MeSH terms
- Antifungal Agents, Candida, Candidiasis, Cytotoxins, Eugenol, Humans, Leukocytes, Mononuclear
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