Synthesis, antifungal activity of caffeic acid derivative esters, and their synergism with fluconazole and nystatin against Candida spp

Janaína de Cássia Orlandi Sardi; Fernanda Patrícia Gullo; Irlan Almeida Freires; Nayla de Souza Pitangui; Maicon Petrônio Segalla; Ana Marisa Fusco-Almeida; Pedro Luiz Rosalen; Luís Octávio Regasini; Maria José Soares Mendes-Giannini

doi:10.1016/j.diagmicrobio.2016.08.002

Synthesis, antifungal activity of caffeic acid derivative esters, and their synergism with fluconazole and nystatin against Candida spp

Diagn Microbiol Infect Dis. 2016 Dec;86(4):387-391. doi: 10.1016/j.diagmicrobio.2016.08.002. Epub 2016 Aug 8.

Authors

Janaína de Cássia Orlandi Sardi¹, Fernanda Patrícia Gullo², Irlan Almeida Freires³, Nayla de Souza Pitangui², Maicon Petrônio Segalla⁴, Ana Marisa Fusco-Almeida², Pedro Luiz Rosalen³, Luís Octávio Regasini⁵, Maria José Soares Mendes-Giannini⁶

Affiliations

¹ Department of Clinical Analysis, Laboratory of Clinical Mycology, Faculty of Pharmaceutical Sciences, UNESP-Univ Estadual Paulista, Araraquara, SP14801-902, Brazil; Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba, SP13414-90, Brazil. Electronic address: [email protected].
² Department of Clinical Analysis, Laboratory of Clinical Mycology, Faculty of Pharmaceutical Sciences, UNESP-Univ Estadual Paulista, Araraquara, SP14801-902, Brazil.
³ Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba, SP13414-90, Brazil.
⁴ Department of Biochemistry and Chemical Technology, Institute of Chemistry, UNESP-Univ Estadual Paulista, Araraquara, SP14800-060, Brazil.
⁵ Department of Biochemistry and Chemical Technology, Institute of Chemistry, UNESP-Univ Estadual Paulista, Araraquara, SP14800-060, Brazil; Department of Chemistry and Environmental Sciences, Institute of Biosciences, Letters and Exact Sciences, São José do Rio Preto, SP15054-000, Brazil.
⁶ Department of Clinical Analysis, Laboratory of Clinical Mycology, Faculty of Pharmaceutical Sciences, UNESP-Univ Estadual Paulista, Araraquara, SP14801-902, Brazil. Electronic address: [email protected].

PMID: 27638348
DOI: 10.1016/j.diagmicrobio.2016.08.002

Abstract

We tested the antifungal potential of caffeic acid and 8 of its derivative esters against Candidaalbicans ATCC 90028 and 9 clinical isolatesand carried out a synergism assay with fluconazole and nystatin. Propyl caffeate (C3) showed the best antifungal activity against the tested strains. When in combination, C3 markedly reduced the MIC of fluconazole and nystatin with synergistic effect up to 64-fold. Finally, C3 showed a high IC₅₀ value and selective indexagainst oral keratinocytes, demonstrating low toxicity against this cell type and selectivity for yeast cells. Further research should confirm its antifungal potential for development of combined therapy to treat C. albicans infections.

Keywords: Antifungal; Caffeic acid; Candida albicans; Synergism.

MeSH terms

Antifungal Agents / chemical synthesis
Antifungal Agents / isolation & purification
Antifungal Agents / pharmacology*
Caffeic Acids / chemical synthesis
Caffeic Acids / isolation & purification
Caffeic Acids / pharmacology*
Caffeic Acids / toxicity
Candida albicans / drug effects*
Candida albicans / isolation & purification
Candidiasis / microbiology
Cells, Cultured
Drug Synergism*
Esters / chemical synthesis
Esters / isolation & purification
Esters / pharmacology*
Esters / toxicity
Fluconazole / pharmacology*
Fluconazole / toxicity
Humans
Inhibitory Concentration 50
Keratinocytes / drug effects
Keratinocytes / physiology
Microbial Sensitivity Tests
Molecular Structure
Nystatin / pharmacology*
Nystatin / toxicity

Substances

Antifungal Agents
Caffeic Acids
Esters
Nystatin
Fluconazole
caffeic acid