title: Enhanced activity of antifungal drugs using natural phenolics against yeast strains of Candida and Cryptococcus.
abstract: OBJECTIVE
  Determine whether certain, natural phenolic compounds enhance activity of commercial antifungal drugs against yeast strains of Candida and Cryptococcus neoformans.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto de Higiene e Medicina Tropical/CREM, Universidade Nova de Lisboa, Portugal.
authors.forename: N C G
authors.initials: NC
authors.lastname: Faria
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: L A P
authors.initials: LA
authors.lastname: Gonçalves
authors.forename: M de L
authors.initials: Mde L
authors.lastname: Martins
authors.forename: K L
authors.initials: KL
authors.lastname: Chan
authors.forename: B C
authors.initials: BC
authors.lastname: Campbell
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010636:Phenols / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae
chemical_list: D000935:Antifungal Agents; D010636:Phenols; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole