Next Article in Journal
Uniting Electroceutical and Cosmeceutical Interventions in Combating Coronavirus Using Ԑ-Poly-l-Lysine
Previous Article in Journal
Novel Amino Acid Derivatives of Quinolines as Potential Antibacterial and Fluorophore Agents
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.
Sci. Pharm. 2020, 88(4), 58; https://doi.org/10.3390/scipharm88040058
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
Show Figures

Figure 1

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.

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.

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.

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop