Human and rat monoamine oxidase-A are differentially inhibited by (S)-4-alkylthioamphetamine derivatives: insights from molecular modeling studies.
Four enantiomerically pure (S)-4-alkylthioamphetamine derivatives were evaluated as monoamine oxidase (MAO) inhibitors using the human and rat isoforms of the enzyme. Molecular dockings were performed in order to gain insights regarding the binding mode of these inhibitors. All compounds were potent and selective MAO-A inhibitors although different rank orders of potencies were observed against the enzymes from different species. This behavior can be rationalized on the basis of different binding modes to each enzyme, as determined in silico. These findings further support the concept that MAO inhibitory activity of novel compounds, determined with enzymes from diverse mammalian species, should be considered with caution if human MAO is the final target to be addressed.
Fierro
Angélica
A
Faculty of Chemistry and Biology, University of Santiago de Chile, Alameda, Santiago, Chile.
Osorio-Olivares
Mauricio
M
Cassels
Bruce K
BK
Edmondson
Dale E
DE
Sepúlveda-Boza
Silvia
S
Reyes-Parada
Miguel
M
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats
D000662:Amphetamines; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase