Natural and synthetic geiparvarins are strong and selective MAO-B inhibitors. Synthesis and SAR studies.
Natural geiparvarin 1 and a number of its analogues were prepared and tested as inhibitors of both monoamine oxidase isoforms, MAO-B and MAO-A. The desmethyl congener 6 of geiparvarin, proved potent and selective MAO-B inhibitor (pIC(50)=7.55 vs 4.62). X-ray crystallography and molecular modelling studies helped the understanding of the observed structure-activity relationships.
Carotti
Angelo
A
Dipartimento Farmaco Chimico, via Orabona 4, I-70125 Bari, Italy. carotti@farmchim.uniba.it
Carrieri
Antonio
A
Chimichi
Stefano
S
Boccalini
Marco
M
Cosimelli
Barbara
B
Gnerre
Carmela
C
Carotti
Andrea
A
Carrupt
Pierre Alain
PA
Testa
Bernard
B
D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D003374:Coumarins; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; C058446:geiparvarin