In vitro activity of natural phenolic compounds against fluconazole-resistant Candida species: a quantitative structure-activity relationship analysis.
AIMS
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.


METHODS AND 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.


SIGNIFICANCE AND IMPACT OF THE STUDY
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.
['Gallucci|M N|MN|', 'Carezzano|M E|ME|', 'Oliva|M M|MM|', 'Demo|M S|MS|', 'Pizzolitto|R P|RP|', 'Zunino|M P|MP|', 'Zygadlo|J A|JA|', 'Dambolena|J S|JS|']
D000935:Antifungal Agents D002175:Candida D000081007:Cymenes D025141:Drug Resistance, Fungal D005054:Eugenol D015725:Fluconazole D006801:Humans D039821:Monoterpenes D010636:Phenols D021281:Quantitative Structure-Activity Relationship D013943:Thymol
natural phenols quantitative structure-activity relationship Candida albicans Candida krusei Candida tropicalis Candida dubliniensis anticandidal activity