P-152 - N-acyl derivatives of 4,6-di-tert-butyl-2-aminophenol protect neutrophils from halogenating stress

Abstract

Hypochlorous acid is an important microbicidal agent mainly formed by neutrophil myeloperoxidase (MPO), however HOCl hyperproduction leads to halogenating stress associated with different diseases. It is necessary to search for substances that can selectively prevent excessive HOCl generation. We synthesized a number of N-acyl derivatives of 4,6-di-tert-butyl-2-aminophenol which exhibit antiradical activity in cell free model systems. The aim of the work is to study the effect of (N-(4,6-di-tert-butyl-2-aminophenol)R, where R=-COCH3 (1), -COC2H5 (2), -COC3H7 (3) on ROS formation, secretory degranulation and viability of neutrophils exposed to HOCl. It has been shown that all compounds in micromolar concentrations reduce neutrophil ROS formation by 75% or more, inhibit MPO secretion and reduce HOCl production by MPO. It has been found that compounds 1–3 effectively intercept HOCl (up to 78%), but do not interact with H2O2. In concentrations of up to 1 μmol/l, compound 1 increases cell survival in the absence of exogenous HOCl, while compounds 2 and 3 do not influence it. Compound 1 in higher concentrations prevents destruction of neutrophils caused by addition of 300 μmol/l HOCl. Thus, compounds 1–3 can be considered as potential cytoprotectors under halogenating stress.