2. Academic Validation
  3. Acetylcholinesterase inhibitory activities and bioguided fractionation of the Ocotea percoriacea extracts: HPLC-DAD-MS/MS characterization and molecular modeling of their alkaloids in the active fraction

Acetylcholinesterase inhibitory activities and bioguided fractionation of the Ocotea percoriacea extracts: HPLC-DAD-MS/MS characterization and molecular modeling of their alkaloids in the active fraction

  • Comput Biol Chem. 2019 Dec:83:107129. doi: 10.1016/j.compbiolchem.2019.107129.
Dayse Santos Almeida Cassiano 1,  Isabella Mary Alves Reis 1,  Isabela de Oliveira Estrela 2,  Humberto Fonseca de Freitas 2,  Samuel Silva da Rocha Pita 2,  Jorge Mauricio David 3,  Alexsandro Branco 4
Affiliations

Affiliations

  • 1 Laboratory of Phytochemistry, Health Department, State University of Feira de Santana (UEFS), Feira de Santana, Bahia, Brazil.
  • 2 Laboratory of Bioinformatics and Molecular Modeling (LaBiMM), Pharmacy College, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil.
  • 3 Chemistry Institute, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil.
  • 4 Laboratory of Phytochemistry, Health Department, State University of Feira de Santana (UEFS), Feira de Santana, Bahia, Brazil. Electronic address: branco@uefs.br.
PMID: 31606587 DOI: 10.1016/j.compbiolchem.2019.107129
Abstract

In vitro acetylcholinesterase activities of the hexane, dichloromethane, ethyl acetate, n-butanol and aqueous extracts of leaves of Ocotea percoriacea Kosterm. (Lauraceae) were evaluated. The bioguided fractionation of the most active extract (dichloromethane) using silica gel open-column chromatography led to an active alkaloidal fraction composed of isocorydine N-oxide, isocorydine N-oxide derivative, palmatine, roemerine and roemerine N-Oxide. The identification of the chemical structure of these compounds was carried out with high-performance liquid chromatography coupled to electrospray ionization multiple-stage mass spectrometry (HPLC-ESI-MS/MS). Aiming to understand their inhibitory activities, these Alkaloids were docked into a 3D model of Electrophorus electricus Acetylcholinesterase (EelAChE) built in the Modeller 9.18 employing homology modeling approach. The results suggest that the Alkaloids had the same binding mode and, possibly, the inhibition mechanism of classic drugs (ex. tacrine and donepezil). The structural difference of these compounds opens a new opportunity for the optimization of leading compounds.

Keywords

Anticholinesterase activity; HPLC-ESI-MS(n); Lauraceae; Molecular modeling; Ocotea percoriaceae.

Figures
Products