NWU Institutional Repository

Inhibition of monoamine oxidase by phthalide analogues

Loading...
Thumbnail Image

Date

Authors

Strydom, Belinda
Bergh, Jacobus J.
Petzer, Jacobus P.

Journal Title

Journal ISSN

Volume Title

Publisher

Elsevier

Abstract

Based on recent reports that the small molecules, isatin and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase (MAO) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues. Phthalide is structurally related to isatin and phthalimide and it is demonstrated here that substitution at C6 of the phthalide moiety yields compounds endowed with high binding affinities to both human MAO isoforms. Among the nineteen homologues evaluated, the lowest IC50 values recorded for the inhibition of MAO-A and -B were 0.096 and 0.0014 lM, respectively. In most instances, C6-substituted phthalides exhibit MAO-B specific inhibition. Among a series of 6-benzyloxyphthalides bearing substituents on the para position of the phenyl ring the general order of potency was CF3 > I > Br > Cl > F > CH3 > H. The results also show that the binding modes of representative phthalides are reversible and competitive at both MAO isoforms. Based on these data, C6-substituted phthalides may serve as leads for the development of therapies for neurodegenerative disorders such as Parkinson’s disease.

Description

Citation

Strydom, B. et al. 2013. Inhibition of monoamine oxidase by phthalide analogues. Bioorganic & medicinal chemistry letters, 23(5):1269-1273. [https://doi.org/10.1016/j.bmcl.2013.01.003]

Endorsement

Review

Supplemented By

Referenced By