Enhanced activity of antifungal drugs using natural phenolics against yeast strains of Candida and Cryptococcus

• Published in: Letters in applied microbiology Vol. 52; no. 5; pp. 506 - 513
• Main Authors: Faria, N.C.G, Kim, J.H, Gonçalves, L.A.P, Martins, M. de L, Chan, K.L, Campbell, B.C
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2011; Blackwell
• Subjects: Amphotericin B; Amphotericin B - pharmacology; antifungal agents; Antifungal Agents - pharmacology; Biological and medical sciences; Candida; Candida - drug effects; Candida albicans; Candida albicans - drug effects; Candida neoformans; Cryptococcus (Hyphomycetes); Cryptococcus neoformans - drug effects; Drug Synergism; fluconazole; Fluconazole - pharmacology; Fundamental and applied biological sciences. Psychology; itraconazole; Itraconazole - pharmacology; Microbial Sensitivity Tests; Microbiology; phenolic; phenolic compounds; Phenols - pharmacology; Saccharomyces cerevisiae; synergism; triazole; yeasts; Fungi; Drug; Antifungal agent; Yeast; Amphotericin B; Applied microbiology; Candida; Phenols; Fungi Imperfecti; Synergism; phenolic; triazole
• ISSN: 0266-8254; 1472-765X
• DOI: 10.1111/j.1472-765X.2011.03032.x

Aims: Determine whether certain, natural phenolic compounds enhance activity of commercial antifungal drugs against yeast strains of Candida and Cryptococcus neoformans. Methods and Results: Twelve natural phenolics were examined for fungicidal activity against nine reference strains of Candida and one of C. neoformans. Six compounds were selected for synergistic enhancement of antifungal drugs, amphotericin B (AMB), fluconazole (FLU) and itraconazole (ITR). Matrix assays of phenolic and drug combinations conducted against one reference strain, each, of Candida albicans and C. neoformans showed cinnamic and benzoic acids, thymol, and 2,3- and 2,5-dihydroxybenzaldehydes (-DBA) had synergistic interactions depending upon drug and yeast strain. 2,5-DBA was synergistic with almost all drug and strain combinations. Thymol was synergistic with all drugs against Ca. albicans and with AMB in C. neoformans. Combinations of benzoic acid or thymol with ITR showed highest synergistic activity. Of 36 combinations of natural product and drug tested, none were antagonistic. Conclusions: Relatively nontoxic natural products can synergistically enhance antifungal drug activity, in vitro. Significance and Impact of the Study: This is a proof-of-concept, having clinical implications. Natural chemosensitizing agents could lower dosages needed for effective chemotherapy of invasive mycoses. Further studies against clinical yeast strains and use of animal models are warranted.