Alkaloids of Phaedranassa dubia (Kunth) J.F. Macbr. and Phaedranassa brevifolia Meerow (Amaryllidaceae) from Ecuador and its cholinesterase-inhibitory activity

Karen Acosta León; Alexandra Inca; Luciana R Tallini; Edison H Osorio; Jessica Robles; Jaume Bastida; Nora H Oleas

doi:10.1016/j.sajb.2020.09.007

Alkaloids of Phaedranassa dubia (Kunth) J.F. Macbr. and Phaedranassa brevifolia Meerow (Amaryllidaceae) from Ecuador and its cholinesterase-inhibitory activity

S Afr J Bot. 2021 Jan:136:91-99. doi: 10.1016/j.sajb.2020.09.007. Epub 2020 Sep 18.

Authors

Karen Acosta León¹, Alexandra Inca¹, Luciana R Tallini^{2

3}, Edison H Osorio⁴, Jessica Robles¹, Jaume Bastida², Nora H Oleas⁵

Affiliations

¹ Grupo de Investigación de Productos Naturales y Farmacia, Facultad de Ciencias, Escuela Superior Politécnica del Chimborazo, Panamericana Sur km 1 1/2, Riobamba EC060155, Ecuador.
² Grup de Productes Naturals, Departament de Biologia, Sanitat i Medi Ambient, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Av. Joan XXIII, 27-31, Barcelona 08028, Spain.
³ Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre RS 90610-000, Brazil.
⁴ Facultad de Ciencias Naturales y Matemáticas, Universidad de Ibagué, Carrera 22 Calle 67, Ibagué 730001, Colombia.
⁵ Centro de Investigación de la Biodiversidad y Cambio Climático (BioCamb) e Ingeniería en Biodiversidad y Recursos Genéticos, Facultad de Ciencias de Medio Ambiente, Universidad Tecnológica Indoamérica, Machala y Sabanilla, Quito EC170301, Ecuador.

Abstract

Alzheimer's disease is considered the most common cause of dementia and, in an increasingly aging population worldwide, the quest for treatment is a priority. Amaryllidaceae alkaloids are of main interest because of their cholinesterase inhibition potential, which is the main palliative treatment available for this disease. We evaluated the alkaloidal profile and the in vitro inhibitory activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) of bulb alkaloid extract of Phaedranassa dubia and Phaedranassa brevifolia collected in Ecuador. Using gas chromatography coupled to mass spectrometry (GC-MS), we identified typical Amaryllidaceae alkaloids in these species, highlighting the presence of lycorine-type alkaloids in P. dubia and haemanthamine/crinine-type in P. brevifolia. The species P. dubia and P. brevifolia showed inhibitory activities against AChE (IC₅₀ values of 25.48 ± 0.39 and 3.45 ± 0.29 μg.mL^-1, respectively) and BuChE (IC₅₀ values of 114.96 ± 4.94 and 58.89 ± 0.55 μg.mL^-1, respectively). Computational experiments allowed us to understand the interactions of the alkaloids identified in these samples toward the active sites of AChE and BuChE. In silico, some alkaloids detected in these Amaryllidaceae species presented higher estimated binding free energy toward BuChE than galanthamine. This is the first study about the alkaloid profile and biological potential of P. brevifolia species.

Keywords: AChE; AChE, Acetylcholinesterase; AE, alkaloid extract; ATCI, acetylthiocholine iodide; Alkaloids; Alzheimer's disease; Amaryllidaceae; BTCI, butyrylthiocholine iodide; BuChE; BuChE, butyrylcholinesterase; CD, circular dichroism; DTNB, (5,5′-dithio-bis-[2-nitrobenzoic acid]); Et2O, diethyl ether; EtOAc, ethyl acetate; GAL, galanthamine; GC-MS, gas chromatography coupled to mass spectrometry; IUCN, International Union for Conservation of Nature; MS, mass spectrometry; MeOH, methanol; Molecular docking; NMR, nuclear magnetic resonance; Phaedranassa; UV, ultraviolet.