title: In vitro activity of natural phenolic compounds against fluconazole-resistant Candida species: a quantitative structure-activity relationship analysis.
abstract: OBJECTIVE
  To evaluate the antifungal activity and to analyse the structure-activity relationship of eleven natural phenolic compounds against four Candida species which are resistant to fluconazole.
  
  
  RESULTS
  Four different species of Candida isolates were used: Candida albicans, Candida krusei, Candida tropicalis and Candida dubliniensis. The phenolic compound carvacrol showed the highest anti-Candida bioactivity, followed by thymol and isoeugenol. The obtained minimum inhibitory concentration (MIC) values obtained were used in a quantitative structure-activity relationship (QSAR) analysis where the electronic, steric, thermodynamic and topological descriptors served as dependent variables. According to the descriptors obtained in this QSAR study, the antifungal activity of phenols has a first action specific character which is based on their interaction with plasma or mitochondrial membranes. The second action is based on a steric descriptor-the maximal and minimal projection of the area-which could explain the inability of some phenolic compounds to be biotransformed to quinones methylene by Candida species.
  
  
  CONCLUSIONS
  According to the descriptors obtained in this QSAR study, the anti-Candida activity of ortho-substituted phenols is due to more than one action mechanism. The anti-Candida activity of phenolic compounds can be predicted by their molecular properties and structural characteristics.
  
  
  CONCLUSIONS
  These results could be employed to predict the anti-Candida activity of new phenolic compounds in the search for new alternatives or complementary therapies to combat against candidiasis.
authors.affiliation: Departamento de Microbiología e Inmunología, Universidad Nacional de Río Cuarto (UNRC), Córdoba, Argentina.
authors.forename: M N
authors.initials: MN
authors.lastname: Gallucci
authors.forename: M E
authors.initials: ME
authors.lastname: Carezzano
authors.forename: M M
authors.initials: MM
authors.lastname: Oliva
authors.forename: M S
authors.initials: MS
authors.lastname: Demo
authors.forename: R P
authors.initials: RP
authors.lastname: Pizzolitto
authors.forename: M P
authors.initials: MP
authors.lastname: Zunino
authors.forename: J A
authors.initials: JA
authors.lastname: Zygadlo
authors.forename: J S
authors.initials: JS
authors.lastname: Dambolena
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D000081007:Cymenes; D025141:Drug Resistance, Fungal; D005054:Eugenol / Q000031:analogs & derivatives / Q000494:pharmacology; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D039821:Monoterpenes / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013943:Thymol / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D000081007:Cymenes; D039821:Monoterpenes; D010636:Phenols; D013943:Thymol; D005054:Eugenol; C036643:isoeugenol; D015725:Fluconazole; C073316:carvacrol
keywords: Candida albicans; Candida dubliniensis; Candida krusei; Candida tropicalis; anticandidal activity; natural phenols; quantitative structure-activity relationship