title: Synthesis, antifungal activity of caffeic acid derivative esters, and their synergism with fluconazole and nystatin against Candida spp.
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 IC50value 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.
authors.affiliation: 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: janasardi@gmail.com.
authors.forename: Janaína de Cássia Orlandi
authors.initials: JC
authors.lastname: Sardi
authors.affiliation: Department of Clinical Analysis, Laboratory of Clinical Mycology, Faculty of Pharmaceutical Sciences, UNESP-Univ Estadual Paulista, Araraquara, SP14801-902, Brazil.
authors.forename: Fernanda Patrícia
authors.initials: FP
authors.lastname: Gullo
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba, SP13414-90, Brazil.
authors.forename: Irlan Almeida
authors.initials: IA
authors.lastname: Freires
authors.affiliation: Department of Clinical Analysis, Laboratory of Clinical Mycology, Faculty of Pharmaceutical Sciences, UNESP-Univ Estadual Paulista, Araraquara, SP14801-902, Brazil.
authors.forename: Nayla de Souza
authors.initials: NS
authors.lastname: Pitangui
authors.affiliation: Department of Biochemistry and Chemical Technology, Institute of Chemistry, UNESP-Univ Estadual Paulista, Araraquara, SP14800-060, Brazil.
authors.forename: Maicon Petrônio
authors.initials: MP
authors.lastname: Segalla
authors.affiliation: Department of Clinical Analysis, Laboratory of Clinical Mycology, Faculty of Pharmaceutical Sciences, UNESP-Univ Estadual Paulista, Araraquara, SP14801-902, Brazil.
authors.forename: Ana Marisa
authors.initials: AM
authors.lastname: Fusco-Almeida
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba, SP13414-90, Brazil.
authors.forename: Pedro Luiz
authors.initials: PL
authors.lastname: Rosalen
authors.affiliation: 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.
authors.forename: Luís Octávio
authors.initials: LO
authors.lastname: Regasini
authors.affiliation: Department of Clinical Analysis, Laboratory of Clinical Mycology, Faculty of Pharmaceutical Sciences, UNESP-Univ Estadual Paulista, Araraquara, SP14801-902, Brazil. Electronic address: gianninimj@gmail.com.
authors.forename: Maria José Soares
authors.initials: MJ
authors.lastname: Mendes-Giannini
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology; D002478:Cells, Cultured; D004357:Drug Synergism; D004952:Esters / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D015725:Fluconazole / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009761:Nystatin / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000935:Antifungal Agents; D002109:Caffeic Acids; D004952:Esters; D009761:Nystatin; D015725:Fluconazole; C040048:caffeic acid
keywords: Antifungal; Caffeic acid; Candida albicans; Synergism