Alzheimeŕs disease (AD) is the most common neurodegenerative disorder, characterized by neuronal loss and cognitive impairment. Currently, very few drugs are available for AD treatment, and a search for new therapeutics is urgently needed. Thus, in the current study, twenty-eight new derivatives of montanine-type Amaryllidaceae alkaloids were synthesized and evaluated for their ability to inhibit human recombinant acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE). Three derivatives (1n, 1o, and 1p) with different substitution patterns demonstrated significant selective inhibitory potency for hAChE (IC50 < 5 μM), and one analog, 1v, showed selective hBuChE inhibition activity (IC50 = 1.73 ± 0.05 μM). The prediction of CNS availability, as disclosed by the BBB score, suggests that the active compounds in this survey should be able pass through the blood-brain barrier (BBB). Cytotoxicity screening and docking studies were carried out for the two most pronounced cholinesterase inhibitors, 1n and 1v.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- alkaloidy chemická syntéza chemie farmakologie MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- hematoencefalická bariéra účinky léků metabolismus MeSH
- isochinoliny chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- molekulární struktura MeSH
- simulace molekulového dockingu * MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
