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Open AccessArticle

BACE1 Inhibitor, Neuroprotective, and Neuritogenic Activities of Melatonin Derivatives

1
Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand
2
Melatonin Research Group, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
3
Faculty of Pharmacy, Srinakharinwirot University, Nakhon-Nayok 26120, Thailand
4
CIIMAR, Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal
5
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
*
Author to whom correspondence should be addressed.
Received: 5 November 2020 / Revised: 1 December 2020 / Accepted: 2 December 2020 / Published: 4 December 2020
Alzheimer’s disease (AD) is a common chronic neurodegenerative disorders. Melatonin (MLT) has been reported to be neuroprotective agent, and its modified structures exhibit potent antioxidant and anti-inflammation activities. Therefore, the activity of MLT and its derivatives against AD was investigated. Herein, the targeted enzymes, such as β-secretase (BACE1) and acetylcholinesterase (AChE), as well as the neuroprotective and neuritogenic effects on P19-derived neurons were evaluated. All the derivatives (15), including MLT, displayed potent inhibitory activity for BACE1, with inhibition values of more than 75% at 5 µM. A molecular docking study predicted that MLT, 5-MT, and 5 bound with BACE1 at catalytic amino acids Asp32 and the flap region, whereas 14 interacted with allosteric residue Thr232 and the flap region. The additional π-π interactions between 2, 3, and 5 with Tyr71 promoted ligand-enzyme binding. In addition, MLT, 1, 3, and 5 significantly protected neuron cells from oxidative stress by increasing the cell viability to 97.95, 74.29, 70.80, and 69.50% at 1 nM, respectively. Moreover, these derivatives significantly induced neurite outgrowth by increasing the neurite length and number. The derivatives 1, 3, and 5 should be thoroughly studied as potential AD treatment and neuroprotective agents. View Full-Text
Keywords: melatonin; Alzheimer’s disease; P19-derived neuron; neurite outgrowth; neuroprotection; molecular docking melatonin; Alzheimer’s disease; P19-derived neuron; neurite outgrowth; neuroprotection; molecular docking
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MDPI and ACS Style

Panyatip, P.; Tadtong, S.; Sousa, E.; Puthongking, P. BACE1 Inhibitor, Neuroprotective, and Neuritogenic Activities of Melatonin Derivatives. Sci. Pharm. 2020, 88, 58. https://0-doi-org.brum.beds.ac.uk/10.3390/scipharm88040058

AMA Style

Panyatip P, Tadtong S, Sousa E, Puthongking P. BACE1 Inhibitor, Neuroprotective, and Neuritogenic Activities of Melatonin Derivatives. Scientia Pharmaceutica. 2020; 88(4):58. https://0-doi-org.brum.beds.ac.uk/10.3390/scipharm88040058

Chicago/Turabian Style

Panyatip, Panyada; Tadtong, Sarin; Sousa, Emília; Puthongking, Ploenthip. 2020. "BACE1 Inhibitor, Neuroprotective, and Neuritogenic Activities of Melatonin Derivatives" Sci. Pharm. 88, no. 4: 58. https://0-doi-org.brum.beds.ac.uk/10.3390/scipharm88040058

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