Journal of medicinal and pharmaceutical chemistry 2009-11-26

Novel compounds designed as antistress agents.

Karyophyllis C Tsiakitzis, Eleni A Rekka, Angeliki P Kourounakis, Panos N Kourounakis

Index: J. Med. Chem. 52 , 7315-8, (2009)

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Abstract

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%.