Screening of unsubstituted cyclic compounds as inhibitors of monoamine oxidases.
A number of unsubstituted aromatic hydrocarbons, azaheterocycles, oxaheterocycles and cyclic ketones were screened for their inhibitory potency towards monoamine oxidases (MAO; EC 1.4.3.4.) A and B. Fair activities (IC50 10-100 microM) and selectivities were found for, e.g. naphthalene, anthracene, phenanthrene, isoquinoline and acridine. The most active inhibitors are oxygen-containing compounds (e.g. coumarin, flavone, dibenzofuran, xanthene, thioxanthone and acridone), with xanthone emerging as a potent (IC50 0.8 microM) and reversible MAO-A inhibitor. All tested inhibitors seem to act in a reversible and time-independent manner.
Institut de Chimie Thérapeutique, Ecole de Pharmacie, Université de Lausanne, Switzerland.
U
U
Thull
B
B
Testa
D000818:Animals; D001921:Brain / Q000201:enzymology; D002867:Chromones / Q000737:chemistry*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000737:chemistry*; D008928:Mitochondria / Q000201:enzymology; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014966:Xanthenes / Q000737:chemistry*; D044004:Xanthones
D002867:Chromones; D005419:Flavonoids; D008996:Monoamine Oxidase Inhibitors; D014966:Xanthenes; D044004:Xanthones; C068514:4-chromanone; C009689:xanthone