Tsiakitzis Karyophyllis C, Rekka Eleni A, Kourounakis Angeliki P, Kourounakis Panos N
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, 54124 Thessaloniki, Greece.
J Med Chem. 2009 Nov 26;52(22):7315-8. doi: 10.1021/jm901169b.
Agents against biologic stress were designed, containing GABA esterified with lorazepam and amidated with (R)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (5) or 3,5-di-tert-butyl-4-hydroxybenzoic acid (6). Compounds 5 and 6 inhibited lipid peroxidation, IC(50) 1.1 and 24 microM. Oxidative damage accompanied stress, 5 and 6 reduced radical attack, uropepsinogen, and morphological changes. Stress increased drug metabolism. Treatment with 5 reduced cytochrome P450 and N-demethylation of erythromycin, 35 and 40%. Compounds 5 and 6 decreased lipidemic indices of hyperlipidemic rats 40-63%.
设计了抗生物应激剂，其含有与劳拉西泮酯化并与（R）-6-羟基-2,5,7,8-四甲基色满-2-羧酸（5）或3,5-二叔丁基-4-羟基苯甲酸（6）酰胺化的γ-氨基丁酸。化合物5和6抑制脂质过氧化，半数抑制浓度（IC50）分别为1.1和24微摩尔。氧化损伤伴随着应激反应，5和6减少了自由基攻击、尿胃蛋白酶原和形态学变化。应激会增加药物代谢。用5治疗可使细胞色素P450和红霉素的N-去甲基化分别降低35%和40%。化合物5和6使高脂血症大鼠的血脂指数降低40%-63%。
