Open AccessInhibitory effects of gallic acid ester derivatives on Saccharomyces cerevisiae multidrug resistance protein Pdr5p
Author(s) -
Pereira Rangel Luciana,
Fritzen Márcio,
Yunes Rosendo Augusto,
Leal Paulo César,
CreczynskiPasa Tânia Beatriz,
FerreiraPereira Antônio
Publication year - 2010
Publication title -
fems yeast research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 92
eISSN - 1567-1364
pISSN - 1567-1356
DOI - 10.1111/j.1567-1364.2010.00603.x
Subject(s) - biology , gallic acid , saccharomyces cerevisiae , multiple drug resistance , inhibitory postsynaptic potential , biochemistry , yeast , antioxidant , antibiotics , neuroscience
Overexpression of the Saccharomyces cerevisiae ABC transporter Pdr5p confers resistance to a range of structurally unrelated xenobiotics. This property allows Pdr5p to be used as a target for novel multidrug resistance reversal reagents or chemosensitizers. Herein, we report the effects of gallic acid derivatives with substitutions either on the ester moiety or in the benzene ring on the activity of Pdr5p. Compounds with a longer side chain (8–16 carbons) resulted in greater inhibition of Pdr5p ATPase. Derivatives with side chains of 8–12 carbons that retained hydroxyl groups on the benzene ring extensively inhibited Pdr5p ATPase activity. These compounds almost completely inhibited the efflux of the Pdr5p fluorescent substrate Rhodamine 6G and at 25 μM chemosensitized the Pdr5p‐overexpressing strain AD124567 to fluconazole (0.4 mg mL −1 ). Gallic acid derivatives may be a new class of Pdr5p inhibitors.