Impact on cholinesterase-inhibition and in silico investigations of sesquiterpenoids from Amazonian Siparuna guianensis Aubl

Regildo M G Martins; Francisco H Xavier-Júnior; Marcela R Barros; Thaís M Menezes; Caio R D de Assis; Ana Cristina G R de Melo; Bruno O Veras; Vany P Ferraz; Antonio A M Filho; Gilvan T Yogui; Ranilson S Bezerra; Gustavo M Seabra; Jorge L Neves; Wanderli P Tadei

doi:10.1016/j.saa.2021.119511

Impact on cholinesterase-inhibition and in silico investigations of sesquiterpenoids from Amazonian Siparuna guianensis Aubl

Spectrochim Acta A Mol Biomol Spectrosc. 2021 May 5:252:119511. doi: 10.1016/j.saa.2021.119511. Epub 2021 Jan 29.

Authors

Affiliations

¹ Post-Graduate in Biotechnology Multi-Institutional Program, PPGBIOTEC, Federal University of Amazonas, UFAM, Av. General Rodrigo Otávio, 3000, Coroado, Manaus, Amazonas, Brazil; Laboratory of Malária and Dengue, National Institute for Amazonian Research, Manaus, AM, Brazil.
² Post-Graduate Program in Biotechnology, University Potiguar Laureate International Universities, Campus Salgado Filho, 59075-000 Natal, RN, Brazil.
³ Biological Chemistry Laboratory, Departamento de Química Fundamental, Universidade Federal de Pernambuco - UFPE, Recife, PE, Brazil.
⁴ Enzymology Laboratory, Department of Biochemistry, Federal University of Pernambuco - UFPE, Recife, PE, Brazil; Laboratory of Organic Compounds in Coastal and Marine Ecosystems - OrganoMAR, Oceanography Department, Federal University of Pernambuco, Recife, PE, Brazil.
⁵ Center for Research and Postgraduate in Science and Technology, Postgraduate Program in Biotechnology and Biodiversity of Amazon, Environmental Chemistry Laboratory, Federal University of Roraima - UFRR, Boa Vista, RR, Brazil.
⁶ Laboratory of Natural Products - LPN, Department of Biochemistry, Federal University of Pernambuco - UFPE, Recife, PE, Brazil.
⁷ Chromatography Laboratory, Department of Chemistry, Institute of Exact Sciences, UFMG, Belo Horizonte, MG, Brazil.
⁸ Laboratory of Organic Compounds in Coastal and Marine Ecosystems - OrganoMAR, Oceanography Department, Federal University of Pernambuco, Recife, PE, Brazil.
⁹ Enzymology Laboratory, Department of Biochemistry, Federal University of Pernambuco - UFPE, Recife, PE, Brazil.
¹⁰ Biological Chemistry Laboratory, Departamento de Química Fundamental, Universidade Federal de Pernambuco - UFPE, Recife, PE, Brazil; Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), School of Pharmacy, University of Florida, Gainesville, FL, USA.
¹¹ Laboratory of Malária and Dengue, National Institute for Amazonian Research, Manaus, AM, Brazil. Electronic address: wptadei@gmail.com.

PMID: 33561686
DOI: 10.1016/j.saa.2021.119511

Abstract

The plant popularly known as "negramina" (Siparuna guianensis Aubl.), member of the family Siparunaceae produces an essential oil that presents several biological activities reported in literature. Here, the essential oil was obtained by hydrodistillation from fresh leaves collected in the state of Roraima, far north of the Amazon. Chemical composition of the essential oil was characterized by gas chromatography coupled to mass spectrometry (GC-MS) and flame ionization detector (GC-FID). The sesquiterpenoid shyobunone and its derivatives were identified as major compounds in the oil (>40%). The effect of S. guianensis essential oil on the acetylcholinesterase (AChE) activity from Crassostrea rhizophorae, Litopenaeus vannamei and Electrophorus electricus was tested by spectrophotometric assays. The essential oil has been identified as an AChE inhibitor. The mechanism of inhibition was investigated as well as spectrofluorimetric interactions between the essential oil and the enzyme. ¹H NMR titration and molecular docking were also investigated. The spectrophotometric results revealed that shyobunone and its derivatives strongly interact with AChE with a kind of non-competitive inhibition. Interaction studies support the results of enzyme inhibition. Molecular coupling predicted that iso-shyobunone is the strongest ligand, corroborated by fluorescence suppression and ¹H NMR titration results. In conclusion, Siparuna guianensis essential oil can be a new source of shyobunone and derivatives capable to reversibly inhibit AChE showing potential neuroprotective properties to be applied in the treatment of Alzheimer's disease.

Keywords: Acetylcholinesterase; Alzheimer’s disease; Essential oil; Shyobunone; Siparuna guianensis Aubl..

MeSH terms

Gas Chromatography-Mass Spectrometry
Molecular Docking Simulation
Oils, Volatile* / pharmacology
Plant Leaves
Sesquiterpenes* / pharmacology

Substances

Oils, Volatile
Sesquiterpenes