Research in natural products: Amaryllidaceae ornamental plants as sources of bioactive compounds

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/12071

Alkaloid Composition and Biological Activities of the Amaryllidaceae Species <i>Ismene amancaes</i> (Ker Gawl.) Herb.

Natural products have always played a significant role in the search for new drugs. One of the most relevant alkaloid-containing plant groups is the Amaryllidaceae family, a source of exclusive structures with a wide variety of pharmacological activities. The aim of this work was to determine the alkaloid composition and biological potential of an extract from the bulbs of an endemic Peruvian Amaryllidaceae species Ismene amancaes (Ker Gawl.) Herb. The alkaloid profiling was carried out by GC-MS, which revealed the presence of 13 compounds, 2 of them unidentified. The plant extract was found to contain high amounts of lycoramine, a galanthamine-type alkaloid. The extract also presented low inhibitory potential against the enzymes AChE and BuChE, with IC50 values of 14.6 ± 0.6 and 37.6 ± 1.4 μg·mL-1, respectively, and good to moderate inhibitory activity against the protozoan Plasmodium falciparum strain FCR-3 (chloroquine-resistant), with IC50 values of 3.78 ± 0.3 μg·mL-1. This is the first report of the alkaloid profile of a plant of the Ismene genus, which could be an interesting source of bioactive compounds. Keywords: Alzheimer’s disease; Amaryllidaceae; Ismene amancaes; Plasmodium falciparum; alkaloids; malaria

Cholinesterase Inhibition Activity, Alkaloid Profiling and Molecular Docking of Chilean Rhodophiala (Amaryllidaceae)

Amaryllidaceae plants are the commercial source of galanthamine, an alkaloid approved for the clinical treatment of Alzheimer's disease. The chemistry and bioactivity of Chilean representatives of Rhodophiala genus from the family of Amaryllidaceae have not been widely studied so far. Ten collections of five different Chilean Rhodophiala were analyzed in vitro for activity against enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) as well as for their alkaloid composition by GC-MS. To obtain an insight into the potential AChE and BuChE inhibitory activity of the alkaloids identified in the most active samples, docking experiments were carried out. Although galanthamine was found neither in aerial parts nor in bulbs of R. splendens, these plant materials were the most active inhibitors of AChE (IC50: 5.78 and 3.62 μg/mL, respectively) and BuChE (IC50: 16.26 and 14.37 μg/mL, respectively). Some 37 known alkaloids and 40 still unidentified compounds were detected in the samples, suggesting high potential in the Chilean Amaryllidaceae plants as sources of both novel bioactive agents and new alkaloids. Keywords: AChE; BuChE; GC-MS; Rhodophiala; alkaloids; molecular docking

Alkaloid Profiling and Cholinesterase Inhibitory Potential of Crinum × amabile Donn. (Amaryllidaceae) Collected in Ecuador

Natural products are one of the main sources for developing new drugs. The alkaloids obtained from the plant family Amaryllidaceae have interesting structures and biological activities, such as acetylcholinesterase inhibition potential, which is one of the mechanisms used for the palliative treatment of Alzheimer's disease symptoms. Herein we report the alkaloidal profile of bulbs and leaves extracts of Crinum × amabile collected in Ecuador and their in vitro inhibitory activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Using Gas Chromatography coupled to Mass Spectrometry (GC-MS), we identified 12 Amaryllidaceae alkaloids out of 19 compounds detected in this species. The extracts from bulbs and leaves showed great inhibitory activity against AChE and BuChE, highlighting the potential of Amaryllidaceae family in the search of bioactive molecules. Keywords: Amaryllidaceae alkaloids, Crinum × amabile, AChE, BuChE, GC-M

Structural Diversity and Biological Potential of Alkaloids from the Genus Hippeastrum, Amaryllidaceae: an Update

The subfamily Amaryllidoideae, Amaryllidaceae, presents an exclusive group of structures known as Amaryllidaceae alkaloids, which have a broad spectrum of biological activities. These plants are classified into 59 genera, including Hippeastrum Herb., which comprises approximately 60 species distributed mainly in South America, being widely used as ornamental plants due to the beauty of its flowers. This review presents an update about the alkaloid profiling of Hippeastrum extracts published between 2012 and 2021, as well as an approach to the biological potential of these compounds. Supplementary information: The online version contains supplementary material available at 10.1007/s43450-021-00211-z. Keywords: Alzheimer's disease; Anti-inflammatory; Antiparasitic; Antitumoral; Cytotoxic; Isoquinoline alkaloids

Chemical profiling and cholinesterase inhibitory activity of five Phaedranassa Herb. (Amaryllidaceae) species from Ecuador

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

Amaryllidaceae plants: a potential natural resource for the treatment of Chagas disease

Background Chagas disease is a neglected zoonosis caused by the parasite Trypanosoma cruzi. It affects over six million people, mostly in Latin America. Drugs available to treat T. cruzi infection have associated toxicity and questionable efficacy at the chronic stage. Hence, the discovery of more effective and safer drugs is an unmet medical need. For this, natural products represent a pool of unique chemical diversity that can serve as excellent templates for the synthesis of active molecules. Methods A collection of 79 extracts of Amaryllidaceae plants were screened against T. cruzi. Active extracts against the parasite were progressed through two cell toxicity assays based on Vero and HepG2 cells to determine their selectivity profile and discard those toxic to host cells. Anti-T. cruzi-specific extracts were further qualified by an anti-amastigote stage assay. Results Two extracts, respectively from Crinum erubescens and Rhodophiala andicola, were identified as highly active and specific against T. cruzi and its mammalian replicative form. Conclusions The results retrieved in this study encourage further exploration of the chemical content of these extracts in search of new anti-T. cruzi drug development starting points

Genetic Diversity and Chemical Profile of Rhodophiala bifida Populations from Brazil

Rhodophiala bifida (Herb.) Traub, Amaryllidaceae, is a species native to South America known to produce alkaloids with potential pharmacological uses such as montanine, which has anti-inflammatory potential. R. bifida could be applied as a natural source of montanine. It is important to understand the genetic diversity of this species in order to assess the sustainable use of this plant. The aim of this study was to evaluate the genetic diversity and chemical profiles of the two known natural populations of R. bifida in Brazil. This report is the first population genetic study of R. bifida. We studied 93 individuals with six Inter-Simple Sequence Repeats (ISSR) primers. A total of 79 loci were amplified. Our results showed high-population structure (Fst = 0.16), with greatest genetic variation at the intrapopulation level. Genetic analyses separated the individuals of R. bifida into two clusters that corresponded to each of the natural populations. Chemical profile evaluation was carried out on dried bulbs, leaves, flowers, and flower scapes by liquid chromatography and mass spectrometry. Montanine and nangustine were the main metabolites identified in both populations. These alkaloids concentrations differed by population and by plant part

Chemical and biological aspects of different species of the genus Clinanthus Herb. (Amaryllidaceae) from South America

The genus Clinanthus Herb. is found in the Andes Region (South America), mainly in Peru, Ecuador, and Bolivia. These plants belong to the Amaryllidaceae family, specifically the Amaryllidoideae subfamily, which presents an exclusive group of alkaloids known as Amaryllidaceae alkaloids that show important structural diversity and pharmacological properties. It is possible to find some publications in the literature regarding the botanical aspects of Clinanthus species, although there is little information available about their chemical and biological activities. The aim of this work was to obtain the alkaloid profile and the anti-cholinesterase activity of four different samples of Clinanthus collected in South America: Clinanthus sp., Clinanthus incarnatus, and Clinanthus variegatus. The alkaloid extract of each sample was analyzed by gas chromatography coupled with mass spectrometry (GC-MS), and their potential against the enzymes acetyl- and butyrylcholinesterase were evaluated. Thirteen alkaloids have been identified among these species, while six unidentified structures have also been detected in these plants. The alkaloid extract of the C. variegatus samples showed the highest structural diversity as well as the best activity against AChE, which was likely due to the presence of the alkaloid sanguinine. The results suggest this genus as a possible interesting new source of Amaryllidaceae alkaloids, which could contribute to the development of new medicines. Keywords: Alzheimer’s disease; Amaryllidaceae alkaloids; Clinanthus incarnatus; Clinanthus sp.; Clinanthus variegatus; alkaloid profiling

The Anti-Cholinesterase Potential of Fifteen Different Species of Narcissus L. (Amaryllidaceae) Collected in Spain

Narcissus L. is a renowned plant genus with a notable center of diversity and is primarily located in the Mediterranean region. These plants are widely recognized for their ornamental value, owing to the beauty of their flowers; nonetheless, they also hold pharmacological importance. In Europe, pharmaceutical companies usually use the bulbs of Narcissus pseudonarcissus cv. Carlton to extract galanthamine, which is one of the few medications approved by the FDA for the palliative treatment of mild-to-moderate symptoms of Alzheimer’s disease. The purpose of this study was to evaluate the potential of these plants in Alzheimer’s disease. The alkaloid extract from the leaves of different species of Narcissus was obtained by an acid-base extraction work-up -procedure. The biological potential of the samples was carried out by evaluating their ability to inhibit the enzymes acetyl- and butyrylcholinesterase (AChE and BuChE, respectively). The species N. jacetanus exhibited the best inhibition values against AChE, with IC50 values of 0.75 ± 0.03 µg·mL−1, while N. jonquilla was the most active against BuChE, with IC50 values of 11.72 ± 1.15 µg·mL−1.Programa Iberoamericano de Ciencia y Tecnologia para el Desarrollo (CYTED, 223RT0140)