TY - JOUR
T1 - Hydroxycoumarins as selective MAO-B inhibitors
AU - Serra, S.
AU - Delogu, G.
AU - Ferino, G.
AU - Cadoni, E.
AU - Matos, M.J.
AU - Vázquez-Rodríguez, S.
AU - Santana, L.
AU - Uriarte, E.
AU - Viña, D.
PY - 2012/1/1
Y1 - 2012/1/1
N2 - A series of 3-aryl-4-hydroxycoumarin derivatives was synthesized with the aim to find out the structural features for the MAO inhibitory activity and selectivity. Methoxy and/or chloro substituents were introduced in the 3-phenyl ring, whereas the position 6 in the coumarin moiety was not substituted or substituted with a methyl group or a chloro atom due to their different electronic, steric and/or lipophilic properties. Most of the synthesized compounds presented MAO-B inhibitory activity. The presence of methoxy and chloro groups, respectively in the para and meta positions of the 3-phenyl ring, have an important influence on the inhibitory activity. Moreover, the presence of a chloro atom in the six position of the moiety (compound 7) improved the inhibitor activity as well as its selectivity against MAO-B compared with iproniazide, used as reference compound. Docking experiments were carried out to understand which are the most energetically preferred orientations adopted by compounds 5, 6 and 7 inside the MAO-B binding pocket.
AB - A series of 3-aryl-4-hydroxycoumarin derivatives was synthesized with the aim to find out the structural features for the MAO inhibitory activity and selectivity. Methoxy and/or chloro substituents were introduced in the 3-phenyl ring, whereas the position 6 in the coumarin moiety was not substituted or substituted with a methyl group or a chloro atom due to their different electronic, steric and/or lipophilic properties. Most of the synthesized compounds presented MAO-B inhibitory activity. The presence of methoxy and chloro groups, respectively in the para and meta positions of the 3-phenyl ring, have an important influence on the inhibitory activity. Moreover, the presence of a chloro atom in the six position of the moiety (compound 7) improved the inhibitor activity as well as its selectivity against MAO-B compared with iproniazide, used as reference compound. Docking experiments were carried out to understand which are the most energetically preferred orientations adopted by compounds 5, 6 and 7 inside the MAO-B binding pocket.
UR - http://www.scopus.com/inward/record.url?scp=84655170309&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2011.11.020
DO - 10.1016/j.bmcl.2011.11.020
M3 - Article
AN - SCOPUS:84655170309
SN - 0960-894X
VL - 22
SP - 258
EP - 261
JO - Bioorganic & Medicinal Chemistry Letters
JF - Bioorganic & Medicinal Chemistry Letters
IS - 1
ER -