Comparative studies on inhibitory properties of semicarbazide-sensitive amine oxidase (SSAO) activity by haloamine compounds

The enzyme mooamine oxidase (MAO, EC 1. 4. 3. 4) exists in mitochondria and another amine oxidase, termed SSAO (EC 1. 4. 3. 6) exists in cell membrane and blood plasma of various mammalian species. These two amine oxidizing enzymes oxidize a lot of bioactive and toxic monoamines. Thus, substrate-preference and inhibitor-specificity overlap to a certain extent. SSAO catalyzes the oxidation of aliphatic primary monoamines to produce toxic aldehydes. SSAO inhibitors have been shown to prevent or reduce such toxicity. Previous work from this laboratory has demonstrated that a haloamine 2-bromoethylamine (2- BEA) was a specific suicide-inhibitor of membrane-bound SSAO without any effect on MAO. In this sutdy, we examined inhibitory effects of other two haloamines, 2- chloro- (2-CEA) and 2-fluoroethylamine (2-FEA) on guinea pig lung SSAO activity and results compared to that of 2-BEA. Among them, only 2-CEA dose- and preincubation time-dependently inhibited SSAO activity, but 2-FEA showed low inhibitory potency to this enzyme. Without preincubation, IC50 values of both compounds were 0. 48mM (2-CEA) and >1mM (2-FEA), respectively and after 60mm preincubation, the IC50 by 2-CEA shifted to a lower value, 15μM. In contrast, 2-FEA strongly inhibited MAO activity with IC50 values of about lOnM before and after 60min preincubation.