Morphinans and isoquinolines: acetylcholinesterase inhibition, pharmacophore modeling, and interaction with opioid receptors.
Following indications from pharmacophore-based virtual screening of natural product databases, morphinan and isoquinoline compounds were tested in vitro for acetylcholinesterase (AChE) inhibition. After the first screen, active and inactive compounds were used to build a ligand-based pharmacophore model in order to prioritize compounds for biological testing. Among the virtual hits tested, the enrichment of actives was significantly higher than in a random selection of test compounds. The most active compounds were biochemically tested for their activity on mu, delta, and kappa opioid receptors.
Schuster
Daniela
D
Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck and Center for Molecular Biosciences Innsbruck-CMBI, Innrain 52a/c, A-6020 Innsbruck, Austria.
Spetea
Mariana
M
Music
Melisa
M
Rief
Silvia
S
Fink
Monika
M
Kirchmair
Johannes
J
Schütz
Johannes
J
Wolber
Gerhard
G
Langer
Thierry
T
Stuppner
Hermann
H
Schmidhammer
Helmut
H
Rollinger
Judith M
JM
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D009019:Morphinans / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D007546:Isoquinolines; D009019:Morphinans; D011957:Receptors, Opioid; D000110:Acetylcholinesterase