<i>Clinanthus microstephium</i>, an Amaryllidaceae Species with Cholinesterase Inhibitor Alkaloids: Structure−Activity Analysis of Haemanthamine Skeleton Derivatives

Adessi, Tonino G.; Borioni, José Luis; Pigni, Natalia B.; Cavallaro, Valéria; Murray, Ana Paula; Puiatti, Marcelo; Oberti, Juan C.; Leiva, Segundo; Nicotra, Viviana E.; García, Manuela E.

doi:10.1002/cbdv.201800662

Cited by 5 publications

(5 citation statements)

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“…Meerow & A. Cano and Clinanthus incarnatus (Kunth) Meerow has recently been reported [ 14 ]: lycorine- and haemenanthamine/crinine-type alkaloids were found in both species, together with galantamine-type alkaloids in C. incarnatus [ 14 ]. Lycorine and haemanthamine-type alkaloids were also reported in Clinanthus microstephium , as well as a homolycorine-type alkaloid [ 15 ].…”

Section: Resultsmentioning

confidence: 99%

Antileishmanial Activity of Clinanthus milagroanthus S. Leiva & Meerow (Amaryllidaceae) Collected in Peru

Soto-Vásquez

Alvarado-García

Osorio

et al. 2023

Plants

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Leishmaniasis is a worldwide infectious parasitic disease caused by different species of protozoa of the genus Leishmania, which are transmitted to animals and humans through the bite of insects of the Psychodidae family. In the present work, the antileishmanial activity of an alkaloid extract of the bulbs of Clinanthus milagroanthus S. Leiva & Meerow (Amaryllidaceae) was evaluated in vitro, in vivo, and in silico against the parasite Leishmania braziliensis, and the chemical profile of the sample was determined by GC-MS analysis. At concentrations of 1, 10, and 100 µg·mL−1, the alkaloid extract presented inhibition percentages of 8.7%, 23.1%, and 98.8%, respectively, against L. braziliensis with a p < 0.05, and IC50 values of 18.5 ± 0.3 µg·mL−1. Furthermore, at a dose of 1.0 mg·kg−1, a greater decrease in lesion size was observed (90%) for in vivo assays, as well as a decrease in infection (96%), finding no significant differences (p > 0.05) in comparison with amphotericin B (92% and 98%, respectively). Eleven alkaloids were identified in C. milagroanthus bulbs: galanthamine, vittatine/crinine, 8-O-demethylmaritidine, anhydrolycorine, 11,12-dehydroanhydrolycorine, hippamine, lycorine, 2-hydroxyanhydrolycorine, 7-hydroxyclivonine, 2α-hydroxyhomolycorine, and 7-hydroxyclivonine isomer. A molecular model of Leishmania braziliensis trypanothione reductase (TRLb) was built using computational experiments to evaluate in silico the potential of the Amaryllidaceae alkaloid identified in C. milagroanthus toward this enzyme. The structures galanthamine, 7-hydroxyclivonine isomer, and crinine showed better estimated free energy of binding than the reference compound, amphotericin B. In conclusion, this is the first in vitro, in vivo, and in silico report about the antileishmanial potential and alkaloid profiling of the extract of C. milagroanthus bulbs, which could become an interesting source of bioactive molecules.

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Section: Resultsmentioning

confidence: 99%

Antileishmanial Activity of Clinanthus milagroanthus S. Leiva & Meerow (Amaryllidaceae) Collected in Peru

Soto-Vásquez

Alvarado-García

Osorio

et al. 2023

Plants

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“…A molecular docking study was performed on 6-hydrohymaritidine by Adessi et al (Adessi et al 2019). The b:a epimeric mixture of 6-hydroxymaritidine, isolated from Hippeastrum reticulatum that showed the highest activity within the studied seven haemanthamine skeleton type alkaloids, was subject to deep pre-and post-docking analysis, including a detailed consideration of the ligand protonation state at physiological pH, and ab-initio DFT calculations for estimation the conformers ratio in water.…”

Section: Docking Studies On Other Amaryllidaceae Alkaloidsmentioning

confidence: 99%

The Amaryllidaceae alkaloids: an untapped source of acetylcholinesterase inhibitors

et al. 2021

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The AChE inhibitory activity of alkaloid extracts and compounds has been in the focus of research on the plants of Amaryllidoideae subfamily since the approval of galanthamine in 2001 by FDA for treatment of mild to moderate Alzheimer's disease. A small fraction of the huge biodiversity of the plants producing Amaryllidaceae alkaloids has been studied as a source of AChE inhibitors. Less than 20% of the known Amaryllidaceae alkaloids have been tested in vitro for their ability to inhibit AChE. Galanthamine, lycorine and haemanthamine are scaffolds for semi-synthesis of potent AChE inhibitors. In the last years, galanthamine has been studied in silico for drug optimization and synthesis of potent dual-binding AChE inhibitors. In silico studies of other Amaryllidaceae alkaloids have also provoked the interest of researchers in the last years. The aim of this article is to provide a comprehensive review on studies of the AChE inhibitory activity of extracts and compounds from the plants of Amaryllidoideae subfamily covering the literature from the last two decades.

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“…Although chemical and pharmacological interest in the genus Clinanthus has increased in recent years, only seven published articles about this genus can be found in the literature, and five of them correspond to the description of new species [ 1 , 9 , 10 , 21 , 22 ]. The first report of a chemical characterization and bioactivity evaluation of a species from this genus was carried out by Adessi and co-workers [ 23 ], who reported the inhibition of AChE and BChE enzymes by the alkaloid 6-hydroxymaritidine, extracted and purified from C. microstephium [ 23 ]. Another study from 2021 reported the chemical characterization and the antiplasmodial activity of two Clinanthus species ( C. incarnatus and C. ruber ) [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Chemical and Biological Aspects of Different Species of the Genus Clinanthus Herb. (Amaryllidaceae) from South America

et al. 2023

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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.

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Clinanthus microstephium, an Amaryllidaceae Species with Cholinesterase Inhibitor Alkaloids: Structure−Activity Analysis of Haemanthamine Skeleton Derivatives

Cited by 5 publications

References 57 publications

Antileishmanial Activity of Clinanthus milagroanthus S. Leiva & Meerow (Amaryllidaceae) Collected in Peru

Antileishmanial Activity of Clinanthus milagroanthus S. Leiva & Meerow (Amaryllidaceae) Collected in Peru

The Amaryllidaceae alkaloids: an untapped source of acetylcholinesterase inhibitors

Chemical and Biological Aspects of Different Species of the Genus Clinanthus Herb. (Amaryllidaceae) from South America

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