Pyridazinone-Substituted Benzenesulfonamides Demonstrate Inhibition of Monoamine Oxidase

Background: The monoamine oxidase (MAO) enzymes are important drug targets. The inhibitors of MAO-A and MAO-B have been used to treat the symptoms of depression and Parkinson’s disease. background: The monoamine oxidase (MAO) enzymes are important drug targets and inhibitors of MAO-A and MAO-B have been used to treat the symptoms of depression and Parkinson’s disease. Methods: A series of seventeen pyridazinone-substituted benzenesulfonamides was synthesized and evaluated as potential inhibitors of human MAO-A and MAO-B. This study is a continuation of our interest in the pharmacological activities of sulfonamide compounds. Results: Among the compounds evaluated, only 10 and 18 demonstrated appreciable inhibition of MAO-B with IC50 values of 2.90 and 4.36 µM, respectively. None of the benzenesulfonamides inhibited the MAO-A isoform. Potential binding orientations and interactions of 10 and 18 with the active site of MAO-B were investigated by computational approaches. method: A series of seventeen pyridazinone-substituted benzenesulfonamides was synthesized and evaluated as potential inhibitors of human MAO-A and MAO-B. This study is a continuation of our interest in the pharmacological activities of sulfonamide compounds. Conclusion: Although these potencies are modest, this study is the first report on MAO inhibition by this class of compounds. Active MAO-B inhibitors may serve as leads for the future discovery of therapeutic agents for neurodegenerative disorders, such as Parkinson’s disease. conclusion: Although these potencies are modest, this study is the first report of MAO inhibition by this class of compounds. Active MAO-B inhibitors may serve as leads for the future discovery of therapeutic agents for neurodegenerative disorders such as Parkinson’s disease.