Monoamine oxidase inhibition by beta-carbolines: a quantum chemical approach.

Monoamine oxidase inhibition by beta-carboline derivatives is related to the energy change, delta E, arising from complex formation between the inhibitor and the enzyme. The energy change was expressed in terms of electronic indexes, which were estimated for a set of aromatic beta-carbolines. The electronic indexes were correlated to the experimental activity indexes by a simplified quantum chemical perturbational treatment with a multiple regression procedure. A characteristic structure for the inhibitor-enzyme complex was derived from the correlation. The molecules are linked by two kinds of bond. One involves the lone pyridine nitrogen pair of beta-carbolines; the other is due to a pi-electronic interaction between the inhibitor indole fragment and a suitable area of the enzyme. Such a model explains the competitive inhibition by beta-carbolines compared to tryptamine and other aromatic amines that are monoamine oxidase substrates.