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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Pyridazinone-substituted Benzenesulfonamides Demonstrate Inhibition of Monoamine Oxidase

Author(s): Anél Petzer, Anton Shetnev, Julia Efimova, Mikhail Korsakov, Sergei Filimonov and Jacobus P. Petzer*

Volume 21, Issue 8, 2024

Published on: 17 April, 2023

Page: [1429 - 1436] Pages: 8

DOI: 10.2174/1570180820666230321090227

Price: $65

Abstract

Background: The monoamine oxidase (MAO) enzymes are important drug targets. 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 MAOB 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.

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.

Keywords: Monoamine oxidase, parkinson’s disease, pyridazinone, benzenesulfonamide, molecular docking, neurotransmission.

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