Monoamine oxidase inhibition by thiazole derivatives substituted with the benzenesulfonamide moiety

Abstract

Based on a report that 1,3,4-oxadiazol-2-ylbenzenesulfonamides act as inhibitors of monoamine oxidase B (MAO-B), the present study explored the effect of replacing the 1,3,4-oxadiazole moiety with a 1,3-thiazole heterocycle. A series of 23 primary sulfonamides were synthesized and evaluated as in vitro inhibitors of the human MAOs. The results showed that the 1,3-thiazolylbenzenesulfonamides were specific inhibitors of MAO-B with the most potent MAO-B inhibitor presenting with an IC₅₀ value of 0.103 µM (3j). Potent MAO-B inhibition was obtained with the substitution of the sulfonamide on the meta position of the phenyl rather than the para position. This study concluded that 1,3-thiazolylbenzenesulfonamides may serve as lead MAO inhibitors for the development of new treatments for disease states such as Parkinson’s disease.