Application of BACE1 immobilized enzyme reactor for the characterization of multifunctional alkaloids from Corydalis cava (Fumariaceae) as Alzheimer's disease targets
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26779945
DOI
10.1016/j.fitote.2016.01.008
PII: S0367-326X(16)30005-3
Knihovny.cz E-zdroje
- Klíčová slova
- Allocryptopine (PubChem CID: 98570), BACE1 inhibitors, Canadaline (PubChem CID: 321459), Canadine (PubChem CID: 443422), Corycavamine (PubChem CID: 90478581), Corycavidine (PubChem CID: 12304033), Corydalis cava alkaloids, Corynoline (PubChem CID: 177014), Corypalmine (PubChem CID: 12304090), Immobilized enzyme reactor, Isocorypalmine (PubChem CID: 10220), PAMPA assay, Scoulerine (PubChem CID: 22955),
- MeSH
- alkaloidy chemie izolace a purifikace MeSH
- Alzheimerova nemoc MeSH
- aspartátové endopeptidasy antagonisté a inhibitory MeSH
- berberinové alkaloidy chemie izolace a purifikace MeSH
- Corydalis chemie MeSH
- enzymy imobilizované antagonisté a inhibitory MeSH
- hematoencefalická bariéra MeSH
- lidé MeSH
- rekombinantní proteiny MeSH
- sekretasy antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkaloidy MeSH
- aspartátové endopeptidasy MeSH
- BACE1 protein, human MeSH Prohlížeč
- berberinové alkaloidy MeSH
- corycavamine MeSH Prohlížeč
- corynoline MeSH Prohlížeč
- enzymy imobilizované MeSH
- rekombinantní proteiny MeSH
- sekretasy MeSH
In our ongoing study focused on Corydalis cava (Fumariaceae), used in folk medicine in the treatment of memory dysfunctions, we have investigated fifteen previously isolated alkaloids for their potential multifunctional activity on Alzheimer's disease (AD) targets. Determination of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibition was carried out using a BACE1-Immobilized Enzyme Reactor (IMER) by validating the assay with a multi-well plate format Fluorescence Resonance Energy Transfer (FRET) assay. Seven alkaloids out of fifteen were found to be active, with (-)-corycavamine (3) and (+)-corynoline (5) demonstrating the highest BACE1 inhibition activity, in the micromolar range, in a concentration dependent manner. BACE1-IMER was found to be a valid device for the fast screening of inhibitors and the determination of their potency. In a permeation assay (PAMPA) for the prediction of blood-brain barrier (BBB) penetration, the most active compounds, (-)-corycavamine (3) and (+)-corynoline (5), were found to be able to cross the BBB. Not all compounds showed activity against glycogen synthase kinase-3β (GSK-3β) and casein kinase-1δ (CK-1δ). On the basis of the reported results, we found that some C. cava alkaloids have multifunctional activity against AD targets (prolyl oligopeptidase, cholinesterases and BACE1). Moreover, we tried to elucidate the treatment effectivity (rational use) of its extract in memory dysfunction in folk medicine.
Centro de Investigaciones Biológicas Avenida Ramiro de Maetzu 9 280 40 Madrid Spain
Medicinal Chemistry Institute CSIC Juan de la Cierva 3 280 06 Madrid Spain
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