Antifungal property of hibicuslide C and its membrane-active mechanism in Candida albicans

Biochimie. 2013 Oct;95(10):1917-22. doi: 10.1016/j.biochi.2013.06.019. Epub 2013 Jun 28.


In this study, the antifungal activity and mode of action(s) of hibicuslide C derived from Abutilon theophrasti were investigated. Antifungal susceptibility testing showed that hibicuslide C possessed potent activities toward various fungal strains and less hemolytic activity than amphotericin B. To understand the antifungal mechanism(s) of hibicuslide C in Candida albicans, flow cytometric analysis with propidium iodide was done. The results showed that hibicuslide C perturbed the plasma membrane of the C. albicans. The analysis of the transmembrane electrical potential with 3,3'-dipropylthiacarbocyanine iodide [DiSC3(5)] indicated that hibicuslide C induced membrane depolarization. Furthermore, model membrane studies were performed with calcein encapsulating large unilamellar vesicles (LUVs) and FITC-dextran (FD) loaded LUVs. These results demonstrated that the antifungal effects of hibicuslide C on the fungal plasma membrane were through the formation of pores with radii between 2.3 nm and 3.3 nm. Finally, in three dimensional flow cytometric contour plots, a reduced cell sizes by the pore-forming action of hibicuslide C were observed. Therefore, the present study suggests that hibicuslide C exerts its antifungal effect by membrane-active mechanism.

Keywords: 3,3′-dipropylthiacarbocyanine; 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; ATCC; American Type Culture Collection; Antifungal effect; CH(2)Cl(2); CLSI; Candida albicans; Clinical and Laboratory Standards Institute; DiSC(3)(5); EtOAc; FD; FITC; FITC–dextran; Hibicuslide C; KCTC; Korean Collection For Type Cultures; LUV; MIC; MTT; MeOH; Membrane-active mechanism; PBS; PC; PE; PI; Phytochemical; dichloromethane; ethyl acetate; fluorescein isothiocyanate; large unilamellar vesicle; methanol; minimum inhibitory concentration; phosphate buffered saline; phosphatidylcholine; phosphatidylethanolamine; phosphatidylinositol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / pharmacology
  • Antifungal Agents / isolation & purification
  • Antifungal Agents / pharmacology*
  • Benzothiazoles
  • Candida albicans / drug effects*
  • Candida albicans / metabolism
  • Candida albicans / ultrastructure
  • Carbocyanines
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Cell Membrane Permeability
  • Dextrans
  • Erythrocytes / cytology
  • Erythrocytes / drug effects
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluoresceins
  • Fluorescent Dyes
  • Hemolysis / drug effects
  • Humans
  • Malvaceae / chemistry*
  • Membrane Potentials / drug effects
  • Phenylpropionates / isolation & purification
  • Phenylpropionates / pharmacology*
  • Plant Extracts / chemistry*
  • Unilamellar Liposomes / chemistry


  • Antifungal Agents
  • Benzothiazoles
  • Carbocyanines
  • Dextrans
  • Fluoresceins
  • Fluorescent Dyes
  • Phenylpropionates
  • Plant Extracts
  • Unilamellar Liposomes
  • fluorescein isothiocyanate dextran
  • hibicuslide C
  • 3,3'-dipropyl-2,2'-thiadicarbocyanine
  • Amphotericin B
  • Fluorescein-5-isothiocyanate
  • fluorexon