Publication:
A novel diterpene agent isolated from Microbispora hainanensis strain CSR-4 and its in vitro and in silico inhibition effects on acetylcholine esterase enzyme

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Issued Date

2020

Resource Type

Article

File Type

application/pdf

ISSN

20452322

DOI

10.1038/s41598-020-68009-y

Other identifier(s)

2-s2.0-85087518686

Rights

Srinakharinwirot University

Rights Holder(s)

Scopus

Bibliographic Citation

Scientific Reports. Vol 10, No.1 (2020)

Suggested Citation

Thawai C., Bunbamrung N., Pittayakhajonwut P., Chongruchiroj S., Pratuangdejkul J., He Y.-W., Tadtong S., Sareedenchai V., Prombutara P., Qian Y. A novel diterpene agent isolated from Microbispora hainanensis strain CSR-4 and its in vitro and in silico inhibition effects on acetylcholine esterase enzyme. Scientific Reports. Vol 10, No.1 (2020). doi:10.1038/s41598-020-68009-y Retrieved from: https://hdl.handle.net/20.500.14740/5631

Title

A novel diterpene agent isolated from Microbispora hainanensis strain CSR-4 and its in vitro and in silico inhibition effects on acetylcholine esterase enzyme

Author(s)

Thawai C.
 Bunbamrung N.
 Pittayakhajonwut P.
 Chongruchiroj S.
 Pratuangdejkul J.
 He Y.-W.
 Tadtong S.
 Sareedenchai V.
 Prombutara P.
 Qian Y.

Abstract

An actinomycete strain CSR-4 was isolated from the rhizosphere soil of Zingiber montanum. Taxonomic characterization revealed strain CSR-4 was a member of the genus Microbispora. Whole-genome sequence analysis exhibited the highest average nucleotide identity (ANI) value (95.34%) and digital DNA–DNA hybridization (DDH) value (74.7%) between strain CSR-4 and the closest relative M. hainanensis DSM 45428T, which was in line with the assignment to same species. In addition, a new diterpene compound, 2α-hydroxy-8(14), 15-pimaradien-17, 18-dioic acid, and nine known compounds were isolated from the ethyl acetate crude extract of fermentation broth. Interestingly, a new diterpene displayed the suppressive effect on the recombinant human acetylcholinesterase (rhAChE) enzymes (IC50 96.87 ± 2.31 μg/ml). In silico studies based on molecular docking and molecular dynamics (MD) simulations were performed to predict a binding mode of the new compound into the binding pocket of the rhAChE enzyme and revealed that some amino acids in the peripheral anions site (PAS), anionic subsite, oxyanion site and catalytic active site (CAS) of the rhAChE have interacted with the compound. Therefore, our new compound could be proposed as a potential active human AChE inhibitor. Moreover, the new compound can protect significantly the neuron cells (% neuron viability = 88.56 ± 5.19%) from oxidative stress induced by serum deprivation method at 1 ng/ml without both neurotoxicities on murine P19-derived neuron cells and cytotoxicity against Vero cells. © 2020, The Author(s).

Subject(s)

Acetylcholinesterase
 Antioxidant
 Cholinesterase inhibitor
 Diterpenoid
 Neuroprotective agent
 Recombinant protein
 RNA 16S
 Actinobacteria
 Animal
 Chemical structure
 Chemistry
 Chlorocebus aethiops
 Classification
 Computer simulation
 Drug effect
 Enzyme active site
 Genetics
 Human
 In vitro study
 Isolation and purification
 Molecular dynamics
 Mouse
 Phylogeny
 Vero cell line
 Acetylcholinesterase
 Actinobacteria
 Animals
 Antioxidants
 Catalytic Domain
 Chlorocebus aethiops
 Cholinesterase Inhibitors
 Computer Simulation
 Diterpenes
 Humans
 In Vitro Techniques
 Mice
 Molecular Dynamics Simulation
 Molecular Structure
 Neuroprotective Agents
 Phylogeny
 Recombinant Proteins
 RNA, Ribosomal, 16S
 Vero Cells

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URI

https://hdl.handle.net/20.500.14740/5631

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Scopus: Year 1983-2021

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