Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 55, Issue 23, Pages 10424-10436Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm301014y
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New series of 4-methyl and 3,4-dimethy1-7-oxycoumarin derivatives (oxadiazoles, thiadiazoles, triazoles, and thiazolidinones) were designed, synthesized, and evaluated for their monoamine oxidase (MAO) A and B inhibiting effect. All the synthesized compounds showed in vitro high affinity and selectivity toward MAO-A isoenzyme, compared to clorgyline and moclobemide, with K-i values on the picomolar range. Moreover, most of the tested compounds displayed MAO inhibitory effect when tested in vivo. The docking experiments carried out on MAO-A and MAO-B structures proved new information about the enzyme-inhibitor interaction and the potential therapeutic application of 7-oxycoumarin scaffold.
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