title: Plumbagin, a Plant-Derived Compound, Exhibits Antifungal Combinatory Effect with Amphotericin B against Candida albicans Clinical Isolates and Anti-hepatitis C Virus Activity.
abstract: Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), the major active constituent of Plumbago indica L., has been shown to be effective against a wide range of infectious microbes. In this study, plumbagin has been evaluated in vitro for its antifungal combinatory effect with amphotericin B against Candida albicans (C. albicans) clinical isolates and anti-hepatitis C virus (HCV) activity. Antifungal activity was determined by broth microdilution method, and combinatory effect was evaluated by checkerboard assay according to ΣFIC indices, while cytotoxicity was determined by MTT assay. Anti-HCV activity was determined in infected Huh7.5 cells using quantitative real-time reverse transcription PCR, and cytotoxicity was evaluated by MTT assay. Plumbagin exerted inhibitory effect against all C. albicans strains with minimum inhibitory concentration values ranging from 7.41 to 11.24 µg/mL. The additive effect of plumbagin when combined with amphotericin B at concentrations of (0.12, 0.13 and 0.19, 1.81 µg/mL, respectively) was obtained against five of seven strains tested with ΣFIC ranging from 0.62 to 0.91. In addition, plumbagin was found to be used safely for topical application when combined with amphotericin B at concentrations corresponding to the additive effect. Plumbagin exerted anti-HCV activity compared with that of telaprevir with IC50 values of 0.57 and 0.01 μM/L, respectively, and selectivity indices SI = 53.7 and SI = 2127, respectively. Our results present plumbagin as a potential therapeutic agent in the treatment of C. albicans and HCV infections. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, 612 42, Brno, Czech Republic.|Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 21 Praha 6 - Suchdol, Prague, Czech Republic.
authors.forename: Sherif T S
authors.identifier: http://orcid.org/0000-0003-3922-2738
authors.initials: ST
authors.lastname: Hassan
authors.affiliation: Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 21 Praha 6 - Suchdol, Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Berchová-Bímová
authors.affiliation: Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, 612 42, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Petráš
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D009285:Naphthoquinones / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D009285:Naphthoquinones; D000666:Amphotericin B; C014758:plumbagin
keywords: HCV infection; antimicrobial agents; fungal infection; natural products; plumbagin