In vitro and in silico analysis of galanthine from Zephyranthes carinata as an inhibitor of acetylcholinesterase

Sierra, Karina; Andrade, Jean Paulo de; Tallini, Luciana R.; Osorio, Edison; Yáñez, Osvaldo; Osorio, Manuel I.; Oleas, Nora H.; García‐Beltrán, Olimpo; Borges, Warley de Souza; Bastida, Jaume; Cortés, Natalie

doi:10.1016/j.biopha.2022.113016

Cited by 10 publications

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“…The alkaloid profile of C. jagus shows that this species produces an exclusive group of crinane-type alkaloids in combination with lycorine-type alkaloids, which agrees with previous phytochemical reports [ 34 , 35 , 36 , 37 ]. E. bonplandii , E. caucana , P. lehmannii, and Z. carinata were shown to produce several crinane, galanthamine, and lycorine-type alkaloids [ 35 , 38 , 39 ], the last with the highest chemodiversity in alkaloids of Amaryllidaceae, which is also in agreement with previous studies [ 40 , 41 , 42 ]. Furthermore, and to the best of our knowledge, this is the first report of phytochemical data for C. tenera , E. formosa , P. ventricosa, and Z. puertoricensis .…”

Section: Discussionsupporting

confidence: 90%

Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches

et al. 2023

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Cancer is a major cause of death and an impediment to increasing life expectancy worldwide. With the aim of finding new molecules for chemotherapeutic treatment of epidemiological relevance, ten alkaloid fractions from Amaryllidaceae species were tested against six cancer cell lines (AGS, BT-549, HEC-1B, MCF-7, MDA-MB 231, and PC3) with HaCat as a control cell line. Some species determined as critically endangered with minimal availability were propagated using in vitro plant tissue culture techniques. Molecular docking studies were carried out to illustrate binding orientations of the 30 Amaryllidaceae alkaloids identified in the active site of some molecular targets involved with anti-cancer activity for potential anti-cancer drugs. In gastric cancer cell line AGS, the best results (lower cell viability percentages) were obtained for Crinum jagus (48.06 ± 3.35%) and Eucharis bonplandii (45.79 ± 3.05%) at 30 µg/mL. The research focused on evaluating the identified alkaloids on the Bcl-2 protein family (Mcl-1 and Bcl-xL) and HK2, where the in vitro, in silico and statistical results suggest that powelline and buphanidrine alkaloids could present cytotoxic activity. Finally, combining experimental and theoretical assays allowed us to identify and characterize potentially useful alkaloids for cancer treatment.

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Section: Discussionsupporting

confidence: 90%

Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches

et al. 2023

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“…Amino acid sequence of 20 oligopeptides and their locations within the primary structure of the yellow pea protein were identified as shown in Table 1. Out of the 20 identified peptides (4-7 amino acids in length), the majority were present in the Although the AChE-inhibitory potency of the standard in the referenced study is lower than what we have reported, the potency of the peptides from our current study is lower than that of the alkaloid galanthine (IC 50 value = 1.96 µg/ml) as reported in the study (29). Another study by Frota et al…”

Section: In Vitro Acetylcholinesterase Inhibitory Activity Of the Syn...supporting

confidence: 44%

In vitro inhibition of acetylcholinesterase activity by yellow field pea (Pisum sativum) protein-derived peptides as revealed by kinetics and molecular docking

et al. 2022

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Compounds with structural similarities to the neurotransmitter (acetylcholine) are mostly used to inhibit the activity of acetylcholinesterase (AChE) in Alzheimer’s disease (AD) therapy. However, the existing drugs only alleviate symptoms of moderate to mild conditions and come with side effects; hence, the search is still on for potent and safer options. In this study, High performance liquid chromatography (HPLC) fractionations of AChE-inhibitory pea protein hydrolysates obtained from alcalase, flavourzyme and pepsin digestions were carried out followed by sequence identification of the most active fractions using mass spectrometry. Subsequently, 20 novel peptide sequences identified from the active fractions were synthesized and five peptides, QSQS, LQHNA, SQSRS, ETRSQ, PQDER (IC50 = 1.53 – 1.61 μg/mL) were selected and analyzed for ability to change AChE protein conformation (fluorescence emission and circular dichroism), kinetics of enzyme inhibition, and enzyme-ligand binding configurations using molecular docking. The kinetics studies revealed different inhibition modes by the peptides with relatively low (<0.02 mM and <0.1 mM) inhibition constant and Michaelis constant, respectively, while maximum velocity was reduced. Conformational changes were confirmed by losses in fluorescence intensity and reduced α-helix content of AChE after interactions with different peptides. Molecular docking revealed binding of the peptides to both the catalytic anionic site and the peripheral anionic site. The five analyzed peptides all contained glutamine (Q) but sequences with Q in the penultimate N-terminal position (LQHNA, SQSRS, and PQDER) had stronger binding affinity. Results from the different analysis in this study confirm that the peptides obtained from enzymatic digestion of pea protein possess the potential to be used as novel AChE-inhibitory agents in AD management.

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“…According to the literature, the results of molecular docking experiments carried out with lycoramine suggest that it has potential application as an AChE inhibitor [ 32 ]. Conversely, a recent study reported low activity for lycoramine in vitro against AChE (IC 50 values of 42.48 ± 1.66 μg·mL −1 ) and no BuChE inhibitory potential [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…The presence of high amounts of the alkaloids lycorine ( 9 ), hippeastrine ( 13 ), and galanthine ( 8 ) could also be responsible for the cholinesterase inhibitory activity of the extract ( Figure 2 ). However, some authors have described that lycorine is inactive against cholinesterase in vitro, with IC 50 values higher than 50 μg·mL −1 [ 33 , 34 ]. The same authors report that galanthine has in vitro AChE inhibitory activity, with IC 50 values of 1.96 ± 0.01 μg·mL −1 , and a different mode of interaction with AChE than that observed for galanthamine in molecular dynamics experiments [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…However, some authors have described that lycorine is inactive against cholinesterase in vitro, with IC 50 values higher than 50 μg·mL −1 [ 33 , 34 ]. The same authors report that galanthine has in vitro AChE inhibitory activity, with IC 50 values of 1.96 ± 0.01 μg·mL −1 , and a different mode of interaction with AChE than that observed for galanthamine in molecular dynamics experiments [ 33 ]. A search of the literature revealed only one scientific publication about the cholinesterase potential of other Ismene species, which reported that an ethanol extract of Ismene festalis was active against AChE and BuChE in a TLC bioautographic assay [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

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

Soto-Vásquez

Rodríguez-Muñoz

Tallini

et al. 2022

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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.

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In vitro and in silico analysis of galanthine from Zephyranthes carinata as an inhibitor of acetylcholinesterase

Cited by 10 publications

References 59 publications

Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches

Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches

In vitro inhibition of acetylcholinesterase activity by yellow field pea (Pisum sativum) protein-derived peptides as revealed by kinetics and molecular docking

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

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