Inhibition of rabbit liver monoamine oxidase by nitro aromatic compounds

Nitrobenzoid, nitroheterocyclic and cyanobenzoid compounds inhibit type B monoamine oxidase. A partially purified enzyme preparation from rabbit liver mitochondria, oxidizing rho-dimethyl-aminobenzylamine as the substrate, was competitively inhibited by nitrobenzoid compounds with K1 values in the range of 0.28 muM for rho-dinitrobenzene to 0.56 muM for rho-nitrobenzoic acid. The potencies of nitrobenzoid compounds were positively correlated with the Hammett sigma value for each substituent on nitrobenzene. Dinitro derivatives were slightly more potent than the corresponding mononitro compounds but not as potent as would be expected from their sigma values. For the nitroheterocyclic compounds, inhibition was also competitive; the lowest K1 was 1.3 muM for 5-nitrofurfural semicarbazone (nitrofurazone). Compounds with cyano groups in place of nitro groups were also inhibitory; the most potent was rho-acetobenzonitrile with a K1 of 1.3 muM. The results of this study indicate that, in addition to nitrobenzoid compounds, other compounds with planar, electron-deficient nuclei are effective inhibitors of type B monoamine oxidase. Although hydrophobic and steric parameters may play some role in inhibition, the predominant factor is the electron-withdrawing power of the ring substituents.