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Molecules 2018, 23(7), 1509; https://doi.org/10.3390/molecules23071509

In Silico Docking and In Vitro Approaches towards BACE1 and Cholinesterases Inhibitory Effect of Citrus Flavanones

1
Department of Food Science and Nutrition, Dong-A University, 37, Nakdong-daero 550 beon-gil, Saha-gu, Busan 49315, Korea
2
Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125, Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea
3
Department of Bioinformatics, KIRBB School of Bioscience, Korea University of Sciences and Technology, 217 Gajung-ro, Yuseong-gu, Daejeon 34113, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Francesca Giampieri
Received: 27 May 2018 / Revised: 19 June 2018 / Accepted: 19 June 2018 / Published: 22 June 2018
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
Full-Text   |   PDF [3333 KB, uploaded 22 June 2018]   |  

Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, distinctively characterized by senile plaques, neurofibrillary tangles, and synaptic loss, finally resulting in neuronal death. β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) and cholinesterases have been identified as therapeutic targets for AD, and the discovery of their inhibitors is of critical importance for developing preventive strategies for AD. To discover natural multi-target compounds possessing BACE1, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory properties, major citrus flavanones including hesperetin, naringenin, and hesperidin were evaluated. In vitro anti-AD activities were performed via BACE1 and cholinesterases inhibition assays, as well as enzyme kinetic predictions. For the design of potential inhibitors of AD-related enzymes, molecular docking analysis was performed. Based on the biological evaluation, hesperidin demonstrated the best inhibitory properties toward BACE1, AChE, and BChE, with IC50 values of 10.02 ± 1.12, 22.80 ± 2.78, and 48.09 ± 0.74 µM, respectively. Kinetic studies revealed that all tested compounds were found to be noncompetitive inhibitors against BACE1 and cholineseterases. In addition, molecular docking studies of these compounds demonstrated negative binding energies for BACE1, AChE, and BChE, indicating high affinity and tight binding capacity for the target enzymes. The present study suggested that the selected citrus flavanones could act together as multiple inhibitors of BACE1, AChE, and BChE, indicating preventive and therapeutic potential against AD. View Full-Text
Keywords: Alzheimer’s disease; BACE1; cholinesterases; in silico docking; citrus flavanones; hesperidin Alzheimer’s disease; BACE1; cholinesterases; in silico docking; citrus flavanones; hesperidin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Lee, S.; Youn, K.; Lim, G.; Lee, J.; Jun, M. In Silico Docking and In Vitro Approaches towards BACE1 and Cholinesterases Inhibitory Effect of Citrus Flavanones. Molecules 2018, 23, 1509.

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