Thiazole derivatives as inhibitors of purified bovine liver mitochondrial monoamine oxidase-B: structure-activity relationships and theoretical study.
Structure-activity relationships were performed on a new series of thiazole derivatives which selectively inactivate monoamine oxidase-B (MAO-B), purified from mitochondrial beef liver. All of the synthesized and tested compounds showed non-competitive inhibition, suggesting the formation of a stable adduct between the tertiary amine function, linked to the thiazolyl derivatives and the active site of the enzyme. The mechanism of MAO-B inhibition is discussed in terms of the Ionization Potential of the amine nitrogen atom and the conformational flexibility of the inhibitors.
Cambria
A
A
Istituto di Scienze Biochimiche e Farmacologiche, University of Catania, Italy.
Raudino
A
A
Geronikaki
A
A
Buemi
G
G
Raciti
G
G
Mazzone
P
P
Guccione
S
S
Ragusa
S
S
D000818:Animals; D020134:Catalytic Domain / Q000187:drug effects; D002417:Cattle; D008930:Mitochondria, Liver / Q000201:enzymology*; D008962:Models, Theoretical; D008968:Molecular Conformation; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D013844:Thiazoles; D008995:Monoamine Oxidase