Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies.
Inhibitors of acetylcholine breakdown by acetylcholinesterase (AChE) constitute the main therapeutic modality for Alzheimer's disease. In the search for natural products with inhibitory action on AChE, this study investigated the activity of saffron extract and its constituents by in vitro enzymatic and molecular docking studies. Saffron has been used in traditional medicine against Alzheimer's disease. Saffron extract showed moderate AChE inhibitory activity (up to 30%), but IC(50) values of crocetin, dimethylcrocetin, and safranal were 96.33, 107.1, and 21.09 μM, respectively. Kinetic analysis showed mixed-type inhibition, which was verified by in silico docking studies. Safranal interacts only with the binding site of the AChE, but crocetin and dimethylcrocetin bind simultaneously to the catalytic and peripheral anionic sites. These results reinforce previous findings about the beneficial action of saffron against Alzheimer's disease and may be of value for the development of novel therapeutic agents based on carotenoid-based dual binding inhibitors.
Department of Cell Culture-Molecular Modeling and Drug Design, Symeonidion Research Center, Theagenion Cancer Hospital, Thessaloniki, Greece. geromchem@yahoo.gr
George D
GD
Geromichalos
Fotini N
FN
Lamari
Magdalini A
MA
Papandreou
Dimitrios T
DT
Trafalis
Marigoula
M
Margarity
Athanasios
A
Papageorgiou
Zacharias
Z
Sinakos
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D001665:Binding Sites; D002338:Carotenoids / Q000737:chemistry / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D027622:Crocus / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D010936:Plant Extracts / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014801:Vitamin A / Q000031:analogs & derivatives
D002800:Cholinesterase Inhibitors; D010936:Plant Extracts; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D000110:Acetylcholinesterase