Application of BACE1 immobilized enzyme reactor for the characterization of multifunctional alkaloids from Corydalis cava (Fumariaceae) as Alzheimer's disease targets
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26779945
DOI
10.1016/j.fitote.2016.01.008
PII: S0367-326X(16)30005-3
Knihovny.cz E-resources
- Keywords
- 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
- Alkaloids chemistry isolation & purification MeSH
- Alzheimer Disease MeSH
- Aspartic Acid Endopeptidases antagonists & inhibitors MeSH
- Berberine Alkaloids chemistry isolation & purification MeSH
- Corydalis chemistry MeSH
- Enzymes, Immobilized antagonists & inhibitors MeSH
- Blood-Brain Barrier MeSH
- Humans MeSH
- Recombinant Proteins MeSH
- Amyloid Precursor Protein Secretases antagonists & inhibitors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Alkaloids MeSH
- Aspartic Acid Endopeptidases MeSH
- BACE1 protein, human MeSH Browser
- Berberine Alkaloids MeSH
- corycavamine MeSH Browser
- corynoline MeSH Browser
- Enzymes, Immobilized MeSH
- Recombinant Proteins MeSH
- Amyloid Precursor Protein Secretases 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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