title: In vitro analysis of flufenamic acid activity against Candida albicans biofilms.
abstract: In a recent high-throughput screen against specific Candida albicans drug targets, several compounds that exhibited non-specific antifungal activity were identified, including the non-steroidal anti-inflammatory drug flufenamic acid (FFA). This study sought to determine the effect of different doses of FFA, alone or in combination with fixed concentrations of the standard antifungal agents amphotericin B (AmB), caspofungin (CAS) or fluconazole (FLU), for the prevention and treatment of C. albicans biofilms. Biofilms were formed in a 96-well microplate followed by evaluation of antifungal activity using the XTT assay. FFA concentrations of ≥512mg/L demonstrated >80% prevention of biofilm formation. FFA concentrations of 1024mg/L demonstrated >85% reduction of mature biofilms. When FFA (≥8mg/L) was used in combination with FLU (32mg/L), antifungal activity increased to 99% for the prevention of biofilm formation. Similarly, when a FFA concentration of ≥8mg/L was used in combination with either AmB (0.25mg/L) or CAS (0.125mg/L), antifungal activity also increased up to 99% for the prevention of biofilm formation. The inhibitory effect of FFA on C. albicans biofilms has not been reported previously, therefore these findings suggest that FFA in combination with traditional antifungals might be useful for the treatment and prevention of C. albicans biofilms.
authors.affiliation: Section of Infectious Diseases, New Mexico Veterans Healthcare System, Albuquerque, NM, USA; Division of Infectious Diseases, University of New Mexico Health Science Center, Albuquerque, NM, USA.
authors.forename: Alba A
authors.initials: AA
authors.lastname: Chavez-Dozal
authors.affiliation: Section of Infectious Diseases, New Mexico Veterans Healthcare System, Albuquerque, NM, USA.
authors.forename: Maximillian
authors.initials: M
authors.lastname: Jahng
authors.affiliation: Division of Infectious Diseases, University of New Mexico Health Science Center, Albuquerque, NM, USA.
authors.forename: Hallie S
authors.initials: HS
authors.lastname: Rane
authors.affiliation: Division of Infectious Diseases, University of New Mexico Health Science Center, Albuquerque, NM, USA.
authors.forename: Kingsley
authors.initials: K
authors.lastname: Asare
authors.affiliation: Division of Infectious Diseases, University of New Mexico Health Science Center, Albuquerque, NM, USA.
authors.forename: Vibhati V
authors.initials: VV
authors.lastname: Kulkarny
authors.affiliation: Section of Infectious Diseases, New Mexico Veterans Healthcare System, Albuquerque, NM, USA; Division of Infectious Diseases, University of New Mexico Health Science Center, Albuquerque, NM, USA.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Bernardo
authors.affiliation: Section of Infectious Diseases, New Mexico Veterans Healthcare System, Albuquerque, NM, USA; Division of Infectious Diseases, University of New Mexico Health Science Center, Albuquerque, NM, USA. Electronic address: SamALee@salud.unm.edu.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Lee
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development*; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology*; D005439:Flufenamic Acid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D005439:Flufenamic Acid
keywords: Antifungal; Biofilm; Candida albicans; Flufenamic acid