The adenosine receptor affinities and monoamine oxidase B inhibitory properties of sulfanylphthalimide analogues

Bioorganic Chemistry
Mietha M Van der WaltJacobus P Petzer

Abstract

Based on a report that sulfanylphthalimides are highly potent monoamine oxidase (MAO) B selective inhibitors, the present study examines the adenosine receptor affinities and MAO-B inhibitory properties of a series of 4- and 5-sulfanylphthalimide analogues. Since adenosine antagonists (A1 and A2A subtypes) and MAO-B inhibitors are considered agents for the therapy of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, dual-target-directed drugs that antagonize adenosine receptors and inhibit MAO-B may have enhanced therapeutic value. The results document that the sulfanylphthalimide analogues are selective for the adenosine A1 receptor over the A2A receptor subtype, with a number of compounds also possessing MAO-B inhibitory properties. Among the compounds evaluated, 5-[(4-methoxybenzyl)sulfanyl]phthalimide was found to possess the highest binding affinity to adenosine A1 receptors with a Ki value of 0.369 μM. This compound is reported to also inhibit MAO-B with an IC50 value of 0.020 μM. Such dual-target-directed compounds may act synergistic in the treatment of Parkinson's disease: antagonism of the A1 receptor may facilitate dopamine release, while MAO-B inhibition may reduce dopamine metabolism....Continue Reading

References

Aug 13, 2003·Neurology·W Bara-JimenezT N Chase
Sep 10, 2011·Neuropharmacology·Rui D S PredigerMaria A B F Vital
Aug 4, 2012·ACS Chemical Neuroscience·Brian C Shook, Paul F Jackson
Jul 31, 2013·Bioorganic Chemistry·Mietha M Van der WaltJacobus P Petzer

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Citations

Sep 24, 2015·Bioorganic & Medicinal Chemistry·Mietha M Van der Walt, Gisella Terre'Blanche

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