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

Resumen

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 <i>in vitro</i> inhibitory activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) of bulb alkaloid extract of <i>Phaedranassa dubia</i> and <i>Phaedranassa brevifolia</i> 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 <i>P. dubia</i> and haemanthamine/crinine-type in <i>P. brevifolia</i>. The species <i>P. dubia</i> and <i>P. brevifolia</i> 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. <i>In silico</i>, 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 <i>P. brevifolia</i> species.