Laboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral/IMPPG, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
FEMS Yeast Res. 2010 May;10(3):244-51. doi: 10.1111/j.1567-1364.2010.00603.x. Epub 2010 Feb 1.
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 muM chemosensitized the Pdr5p-overexpressing strain AD124567 to fluconazole (0.4 mg mL(-1)). Gallic acid derivatives may be a new class of Pdr5p inhibitors.
酿酒酵母 ABC 转运蛋白 Pdr5p 的过表达赋予了其对一系列结构上无关的异生物质的抗性。这种特性使得 Pdr5p 可以被用作新型多药耐药逆转试剂或化学增敏剂的靶标。在此，我们报告了取代酯部分或苯环的没食子酸衍生物对 Pdr5p 活性的影响。具有较长侧链（8-16 个碳原子）的化合物导致 Pdr5p ATP 酶的抑制作用更大。苯环上保留羟基的具有 8-12 个碳原子的侧链衍生物可广泛抑制 Pdr5p ATP 酶活性。这些化合物几乎完全抑制了 Pdr5p 荧光底物 Rhodamine 6G 的外排，并且在 25 μM 时使 Pdr5p 过表达的 AD124567 菌株对氟康唑（0.4 mg mL（-1））敏感。没食子酸衍生物可能是一类新的 Pdr5p 抑制剂。
