Application of BACE1 immobilized enzyme reactor for the characterization of multifunctional alkaloids from Corydalis cava (Fumariaceae) as Alzheimer's disease targets

Fitoterapia
Jakub ChlebekVincenza Andrisano

Abstract

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 alkalo...Continue Reading

References

Dec 14, 2001·The Journal of Biological Chemistry·Fiona Grüninger-LeitchHeinz Döbeli
Apr 2, 2003·European Journal of Medicinal Chemistry·Li DiGuy T Carter
Mar 23, 2004·Current Medicinal Chemistry·M Alonso, A Martinez
Apr 28, 2006·The Journal of Pharmacy and Pharmacology·Kornkanok IngkaninanNantaka Khorana
Jun 29, 2006·The Journal of Biological Chemistry·Florian PlattnerK Peter Giese
Mar 16, 2007·Assay and Drug Development Technologies·Andrea BakiGyörgy M Keserü
Jun 15, 2007·The Journal of Biological Chemistry·Diane P HangerBrian H Anderton
Jun 19, 2007·Journal of Ethnopharmacology·Anne AdsersenAnna K Jäger
Nov 14, 2007·Bioorganic & Medicinal Chemistry Letters·Lorna PiazziAngela Rampa
Jan 10, 2008·Journal of Medicinal Chemistry·Andrea CavalliCarlo Melchiorre
Oct 15, 2008·Expert Opinion on Therapeutic Targets·Akanksha KannojiVitukudi N Balaji
Oct 28, 2008·Journal of Chromatography. a·Manuela BartoliniVincenza Andrisano
Apr 16, 2009·British Journal of Pharmacology·Geetha Vani RayasamAbhijit Ray
Aug 5, 2009·Biological & Pharmaceutical Bulletin·Hyun Ah JungJae Sue Choi
Aug 14, 2009·Journal of Pharmaceutical and Biomedical Analysis·Francesca Mancini, Vincenza Andrisano
Jun 26, 2010·Medicinal Research Reviews·Daniel I PerezAna Martinez
Apr 26, 2011·Drug Discovery Today·Peter Aadal NielsenGunnar Andersson
Dec 7, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Vasudevan ManiAbu Bakar Abdul Majeed
Apr 17, 2012·Journal of Pharmaceutical and Biomedical Analysis·Angela De SimoneVincenza Andrisano
Dec 22, 2014·Steroids·Cheuk W LamSamir A Ross
Apr 12, 2015·Fitoterapia·Lucie CahlíkováKateřina Macáková

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Citations

Dec 28, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ting GuNian-Guang Li
Dec 21, 2017·International Journal of Molecular Sciences·Heyjin LeeJae-Ha Ryu
Nov 9, 2018·International Journal of Molecular Sciences·Phurpa WangchukDenise L Doolan
Oct 14, 2019·Journal of Pharmaceutical and Biomedical Analysis·Angela De SimoneVincenza Andrisano
Aug 15, 2021·International Journal of Biological Macromolecules·Robert NawrotAnna Goździcka-Józefiak

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