Publication:
Bace1 inhibitor, neuroprotective, and neuritogenic activities of melatonin derivatives

1
0

Issued Date

2020

Resource Type

Article

File Type

application/pdf

ISSN

368709

DOI

10.3390/scipharm88040058

Other identifier(s)

2-s2.0-85098981013

Rights

Srinakharinwirot University

Rights Holder(s)

Scopus

Bibliographic Citation

Scientia Pharmaceutica. Vol 88, No.4 (2020), p.1-13

Suggested Citation

Panyatip P., Tadtong S., Sousa E., Puthongking P. Bace1 inhibitor, neuroprotective, and neuritogenic activities of melatonin derivatives. Scientia Pharmaceutica. Vol 88, No.4 (2020), p.1-13. doi:10.3390/scipharm88040058 Retrieved from: https://hdl.handle.net/20.500.14740/5568

Title

Bace1 inhibitor, neuroprotective, and neuritogenic activities of melatonin derivatives

Author(s)

Panyatip P.
 Tadtong S.
 Sousa E.
 Puthongking P.

Abstract

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 (1–5), 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 1–4 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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Subject(s)

Acetylcholinesterase
 Amino acid
 Antifungal agent
 Antioxidant
 Beta secretase
 Beta secretase 1
 Glutathione peroxidase
 Glycine
 Melatonin derivative
 Neuroprotective agent
 Protein p19
 Quercetin
 Retinoic acid
 Tau protein
 Threonine
 Allosterism
 Alzheimer disease
 Animal cell
 Article
 Catalysis
 Cell viability
 Chemical structure
 Chloroplast
 Circular dichroism
 Controlled study
 Crystal structure
 Cytotoxicity
 Drug synthesis
 Electrophorus electricus
 Enzyme activity
 Enzyme binding
 Fetal bovine serum
 Genetic algorithm
 Human
 Human cell
 Hydrogen bond
 IC50
 Inflammation
 Molecular docking
 Molecular interaction
 MTT assay
 Nerve cell
 Neurite outgrowth
 Neuroprotection
 Neurotoxicity
 Nonhuman
 Oxidative stress
 Quantitative structure activity relation
 Static electricity

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URI

https://hdl.handle.net/20.500.14740/5568

Collections

Scopus: Year 1983-2021

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