Search

It is estimated that 50 million people in the world live with dementia, 60–70% of whom suffer from Alzheimer's disease (AD). Different factors are involved in the development of AD, including a reduction in the cholinergic neurotransmission level. The Amaryllidaceae plant family contains an exclusive, large, and still understudied alkaloid group characterized by a singular skeleton arrangement and a broad spectrum of biological activities. The chemistry and biodiversity of Ecuadorian representatives of the Phaedranassa genus (Amaryllidaceae) have not been widely studied. In this work, five Ecuadorian Phaedranassa species were examined in vitro for their activity towards the enzymes acetyl- (AChE) and butyrylcholinesterase (BuChE), and the alkaloid profile of bulb extracts was analyzed by GC-MS. The species Phaedranassa cuencana and Phaedranassa dubia showed the most AChE and BuChE inhibitory activity, respectively. To obtain insight into the potential role of the identified alkaloids in these inhibitory effects, docking experiments were carried out, and cantabricine showed in silico inhibitory activity against both cholinesterase structures. Our results show that Amaryllidaceae species from Ecuador are a potential source of new drugs for the palliative treatment of AD. [ABSTRACT FROM AUTHOR]

• The role of Amaryllidaceae species from Ecuador as source of new drugs. • High amount of lycorine-type alkaloids in Phaedranassa dubia by GC-MS. • In vitro potential of Phaedranassa brevifolia as cholinesterase inhibitor. • Theoretical inhibitory activity of alkaloids against cholinesterase enzymes. 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 (IC 50 values of 25.48 ± 0.39 and 3.45 ± 0.29 μg.mL−1, respectively) and BuChE (IC 50 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. [ABSTRACT FROM AUTHOR]