Caltabiano M M, Poste G, Greig R G
Department of Cell Biology, Smith Kline & French Laboratories, Philadelphia, PA 19101.
Biochem Pharmacol. 1988 Nov 1;37(21):4089-93. doi: 10.1016/0006-2952(88)90100-1.
Challenge of human cells with auranofin, 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S-triethylpho sphine gold(I) (Ridaura), a gold-containing compound approved by the FDA for the treatment of rheumatoid arthritis, induces the specific synthesis of a 32-kD stress protein (p32) [Caltabiano et al., Biochem. biophys. Res. Commun. 138, 1074 (1986)]. To establish a structure-activity relationship for this effect, a series of auranofin ligands, gold analogs, and other anti-arthritic agents were examined for their abilities to stimulate p32 synthesis. The results indicate that the gold atom is necessary for enhanced expression of p32. However, the structure of co-ordinated ligands also affected potency, and gold complexes bearing several phosphine or thiosugar groups exhibited the greatest activity. These data indicate that the distinct potencies of auranofin analogs probably reflect their membrane permeability and subsequent delivery of pharmacologically active concentrations of gold to the cytoplasmic compartment.
用金诺芬（瑞得，2,3,4,6-四-O-乙酰基-1-硫代-β-D-吡喃葡萄糖基-S-三乙膦金(I)）对人细胞进行刺激，金诺芬是一种经美国食品药品监督管理局（FDA）批准用于治疗类风湿性关节炎的含金化合物，可诱导特异性合成一种32-kD应激蛋白（p32）[卡尔塔比亚诺等人，《生物化学与生物物理研究通讯》138, 1074 (1986)]。为了建立这种效应的构效关系，研究了一系列金诺芬配体、金类似物和其他抗关节炎药物刺激p32合成的能力。结果表明，金原子对于p32的增强表达是必需的。然而，配位配体的结构也影响效力，带有多个膦或硫糖基团的金配合物表现出最大活性。这些数据表明，金诺芬类似物的不同效力可能反映了它们的膜通透性以及随后将药理活性浓度的金递送至细胞质区室的情况。
