Showing papers on "Amaryllidaceae Alkaloids published in 2016"

Synthesis of Amaryllidaceae Constituents and Unnatural Derivatives.

Abstract: This update covers the syntheses of Amaryllidaceae alkaloids since the publication of the last major review in 2008. A short summary of past syntheses and their step count is provided for the major constituents; pancratistatin, 7-deoxypancratistatin, narciclasine, lycoricidine, lycorine, and for other natural constituents, as well as for unnatural derivatives. Discussion of biological activities is provided for unnatural derivatives. Future prospects and further developments in this area are covered at the end of the review. The literature is covered to the end of August 2015.

The Amaryllidaceae alkaloids: biosynthesis and methods for enzyme discovery

Abstract: Amaryllidaceae alkaloids are an example of the vast diversity of secondary metabolites with great therapeutic promise. The identification of novel compounds in this group with over 300 known structures continues to be an area of active study. The recent identification of norbelladine 4'-O-methyltransferase (N4OMT), an Amaryllidaceae alkaloid biosynthetic enzyme, and the assembly of transcriptomes for Narcissus sp. aff. pseudonarcissus and Lycoris aurea highlight the potential for discovery of Amaryllidaceae alkaloid biosynthetic genes with new technologies. Recent technical advances of interest include those in enzymology, next generation sequencing, genetic modification, nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS).

CYP96T1 of Narcissus sp. aff. pseudonarcissus Catalyzes Formation of the Para-Para' C-C Phenol Couple in the Amaryllidaceae Alkaloids

Abstract: The Amaryllidaceae alkaloids are a family of amino acid derived alkaloids with many biological activities; examples include haemanthamine, haemanthidine, galanthamine, lycorine, and maritidine. Central to the biosynthesis of the majority of these alkaloids is a C-C phenol-coupling reaction that can have para-para’, para-ortho’, or ortho-para’ regiospecificity. Through comparative transcriptomics of Narcissus sp. aff. pseudonarcissus, Galanthus sp., and Galanthus elwesii we have identified a para-para’ C-C phenol coupling cytochrome P450, CYP96T1, capable of forming the products (10bR,4aS)-noroxomaritidine and (10bS,4aR)-noroxomaritidine from 4’-O-methylnorbelladine. CYP96T1 was also shown to catalyzed formation of the para-ortho’ phenol coupled product, N-demethylnarwedine, as less than 1 % of the total product. CYP96T1 co-expresses with the previously characterized norbelladine 4’-O-methyltransferase. The discovery of CYP96T1 is of special interest because it catalyzes the first major branch in Amaryllidaceae alkaloid biosynthesis. CYP96T1 is also the first phenol-coupling enzyme characterized from a monocot.

Antiproliferative activities of Amaryllidaceae alkaloids from Lycoris radiata targeting DNA topoisomerase I.

Abstract: Crude Amaryllidaceae alkaloids (AAs) extracted from Lycoris radiata are reported to exhibit significant anti-cancer activity. However, the specific alkaloids responsible for the pharmacodynamic activity and their targets still remain elusive. In this context, we strived to combine affinity ultrafiltration with topoisomerase I (Top I) as a target enzyme aiming to fish out specific bioactive AAs from Lycoris radiata. 11 AAs from Lycoris radiata were thus screened out, among which hippeastrine (peak 5) with the highest Enrichment factor (EF) against Top I exhibited good dose-dependent inhibition with IC50 at 7.25 ± 0.20 μg/mL comparable to camptothecin (positive control) at 6.72 ± 0.23 μg/mL. The molecular docking simulation further indicated the inhibitory mechanism between Top I and hippeastrine. The in vitro antiproliferation assays finally revealed that hippeastrine strongly inhibited the proliferation of HT-29 and Hep G2 cells in an intuitive dose-dependent manner with the IC50 values at 3.98 ± 0.29 μg/mL and 11.85 ± 0.20 μg/mL, respectively, and also induced significant cellular morphological changes, which further validated our screening method and the potent antineoplastic effects. Collectively, these results suggested that hippeastrine could be a very promising anticancer candidate for the therapy of cancer in the near future.

Alkaloids with Activity against the Zika Virus Vector Aedes aegypti (L.)-Crinsarnine and Sarniensinol, Two New Crinine and Mesembrine Type Alkaloids Isolated from the South African Plant Nerine sarniensis.

Abstract: Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types, named crinsarnine (1) and sarniensinol (2), were isolated from the dried bulbs of Nerine sarniensis together with bowdensine (3), sarniensine (4), hippadine (5) and 1-O-acetyl-lycorine (6) Crinsarnine (1) and sarniensinol (2) were characterized using spectroscopic and chiroptical methods as (1S,2S,4aR,10bS)-2,7-dimethoxy-1,2,3,4,4a,6-hexahydro-5,11b-ethano[1,3]dioxolo-[4,5-j]phenanthridin-1-yl acetate and (6-(3aR,4Z,6S,7aS)-6-methoxy-1-methyl-2,3,3a,6,7,7a-hexa-hydro-1H-indol-3a-yl)benzo[d][1,3]dioxol-5-yl)methanol, respectively Furthermore, the complete spectroscopic characterization of bowdensine (3) is reported for the first time Compounds 1–6 were evaluated against the Orlando reference strain of Aedes aegypti None of compounds showed mortality against 1st instar Ae aegypti larvae at the concentrations tested In adult topical bioassays, only 1 displayed adulticidal activity with an LD50 = 229 ± 0049 μg/mosquito As regards the structure-activity relationship, the pretazettine and crinine scaffold in 2 and 4 and in 1 and 3 respectively, proved to be important for their activity, while the pyrrole[de]phenanthridine scaffold present in 5 and 6 was important for their reactivity Among the pretazettine group compounds, opening of the B ring or the presence of a B ring lactone as well as the trans-stereochemistry of the A/B ring junction, appears to be important for activity, while in crinine-type alkaloids, the substituent at C-2 seems to play a role in their activity

The Biological Activity of Alkaloids from the Amaryllidaceae: From Cholinesterases Inhibition to Anticancer Activity:

Abstract: Modern research has shown that Amaryllidaceae alkaloids represent a rich reservoir of potential small chemical molecules exhibiting several medicinal properties through various mechanisms. Among th...

Cytotoxic Alkaloid Constituents of the Amaryllidaceae

Abstract: The Amaryllidaceae alkaloids are a group of isoquinoline alkaloids with a distinct array of structural diversity. These compounds have attracted widespread attention due to their manifold biological properties, of which their significance in motor neuron disease through the clinical representative galanthamine is most striking. The cytotoxic potential of Amaryllidaceae alkaloids has also been gaining ground following the advancement of its phenanthridones pancratistatin and narciclasine into clinical trials. This progress has sparked considerable interest in this plant family as a sustainable source of potential anticancer chemotherapeutics. Given this background, this review seeks to (1) examine the cytotoxic effects of Amaryllidaceae alkaloids in cancer cell lines, (2) provide a structural and pharmacophoric basis to these effects, and (3) highlight the various molecular mechanisms behind these activities.

Isolation of Amaryllidaceae alkaloids from Nerine bowdenii W. Watson and their biological activities

Abstract: Twenty-two isoquinoline alkaloids (1–22) were isolated from fresh bulbs of Nerine bowdenii (Amaryllidaceae) by standard chromatographic methods. The chemical structures were elucidated by MS, and 1D and 2D NMR spectroscopic analyses, and by comparison with literature data. 6-O-Demethylbelladine (11) and 4′-O-demethylbelladine (12) are reported here for the first time. Compounds isolated in sufficient amounts were evaluated for their acetylcholinesterase, and butyrylcholinesterase inhibition activity using Ellman's method. In the prolyl oligopeptidase assay, Z-Gly-Pro-p-nitroanilide was used as substrate. Untested alkaloids were also screened for their cytotoxic activity against p53-mutated Caco-2 and HT-29 colorectal adenocarcinoma cells. At the same time, healthy small intestine cells FH-74 Int were used to determine overall toxicity against noncancerous cells. The crinine-type alkaloid buphanisine (7) demonstrated interesting cytotoxicity against both tested cancer cell lines with IC50 values of 8.59 ± 0.15 μM for Caco-2 and 5.32 ± 1.70 μM for HT-29.

Identification of Alkaloids from Hippeastrum aulicum (Ker Gawl.) Herb. (Amaryllidaceae) Using CGC-MS and Ambient Ionization Mass Spectrometry (PS-MS and LS-MS)

Abstract: Amaryllidaceae alkaloids are well-known isoquinolines which have demonstrated a wide range of biological activities such as antiviral, anticancer, acetylcholinesterase inhibition, antimalarial, among others. Mass spectrometry (MS) studies based on capillary gas chromatography (CGC), paper spray (PS), and leaf spray (LS) ionization were carried out for alkaloid investigation of the native Brazilian species Hippeastrum aulicum, along with nuclear magnetic resonance (NMR) techniques. Thirty-one alkaloids were identified including the new compound haemanthamine N-oxide. The results from PS- and LS-MS techniques were consistent with those observed in CGC-MS analysis. To the best of our knowledge, it is the first study combining NMR, CGC-MS and the ambient ionization-mass spectrometry (PS- and LS-MS) on Amaryllidaceae plants.

Heterocyclic Amaryllidaceae Alkaloids: Biosynthesis and Pharmacological Applications.

Abstract: Amaryllidaceae alkaloids (AAs), which are natural heterocyclic compounds, are isolated from Amaryllidaceae plants such as narcissus, snowdrop and spider lily. AAs have been extensively studied due to their multiple pharmacological properties. Nevertheless, knowledge of AA synthesis in plants is lacking and most genes encoding enzymes involved in their production remain unknown. AAs are structurally complex compounds which are challenging for total chemical synthesis that is economically viable. Therefore the understanding of AA biosynthesis could allow for the development of biotechnologies for the production of natural AAs or analogues, maintaining or improving their pharmacological properties. In this review, we describe the progress regarding the biosynthesis and pharmacological properties of AAs. The most recent developments in neurological, anti-cancer and anti-microbial bioactivities of heterocyclic AAs are covered.

In vivo Cytotoxicity Studies of Amaryllidaceae Alkaloids.

Abstract: The plant family Amaryllidaceae is recognizable for its esthetic floral characteristics, its widespread usage in traditional medicine as well as its unique alkaloid principles. Few alkaloid-producing families rival the Amaryllidaceae in terms of the diversity of its structures as well as their wide applicability on the biological landscape. In particular, cytotoxic effects have come to be a dominant theme in the biological properties of Amaryllidacea alkaloids. To this extent, a significant number of structures have been subjected to in vitro studies in numerous cell lines from which several targets have been identified as promising chemotherapeutics. By contrast, in vivo models of study involving these alkaloids have been carried out to a lesser extent and should prove crucial in the continued development of a clinical target such as pancratistatin. This survey examines the cytotoxic effects of Amaryllidaceae alkaloids in vivo and contrasts these against the corresponding in vitro effects.

Concise Total Syntheses of (±)-Joubertiamine, (±)-O-Methyl­joubertiamine, (±)-3′-Methoxy-4′-O-methyljoubertiamine, (±)-Mesembrane, and (±)-Crinane

Abstract: A method to access cis-3a-aryloctahydroindole alkaloids has been developed through a key strategy involving Eschenmoser–Claisen rearrangement of allylalcohol. This approach gives us an opportunity to access the all-carbon quaternary center required for cis-3a-aryloctahydroindole alkaloids. Subsequent simple allylic oxidation of Eschenmoser–Claisen products and synthetic elaborations (reductions/oxidations) enabled the total syntheses of the title compounds to be completed in good yields in a few steps. The strategic viability was further tested in the total syntheses of Amaryllidaceae alkaloids (±)-mesembrane and (±)-crinane. Towards this end, we synthesized advanced intermediate keto-aldehydes from Eschenmoser–Claisen rearrangement products through iodolactonization followed by elaboration involving reduction and oxidation steps.

In Vitro Micropropagation and Alkaloid Production of Galanthus transcaucasicus Fomin

Abstract: Background: In this study we report the production and identification of alkaloid compounds from tissue culture derived from bulb scales of Galanthus transcaucasicus Fomin (Amaryllidaceae), a medicinally important plant. Methods: Explants were prepared from bulb scales of G. transcaucasicus in vitro. The alkaloid compounds were extracted and analyzed by GC/MS. Results: Isolation of the alkaloid fraction of the produced bulblets and its GC/MS analysis led to the identification of an Amaryllidaceae alkaloid homolycorin. Moreover, galantamine was not detected in the alkaloid fraction. Conclusion: At the present study we report the first micropropagation work on G. transcaucasicus together with the isolation of alkaloid homolycorine from in vitro produced bulblets. The results indicated that G. transcaucasicus bulblets produce Amaryllidaceae alkaloids and could be a new source of bioactive compounds for possible pharmaceutical applications. Also, described method could be used for micropropagation of plantlets from G. transcaucasicus.

Phytochemical and Biological Investigation of Clivia nobilis Flowers Cultivated in Egypt.

Abstract: Amaryllidaceae is a well-known family for its high alkaloidal content. These alkaloids comprise a unique group of bases that have been found to occur in this family. The Amaryllidaceae alkaloids represent a large and still expanding group of isoquinoline alkaloids, the majority of which are not known to occur in any other family of plants. This article reports on the phytochemical investigation of the alkaloidal content of the flowers of clivia nobilis cultivated in Egypt which resulted in the isolation of four alkaloids; lycorine with pyrrolo{de} phenanthridine nucleus (lycorine-type) which is the common alkaloid of the amaryllidaceae family, clivatine and nobilisine, both with [2]benzopyrano (3,4-g) indole nucleus (lycoreninetype) and (+) 8-O-demethylmaritidine with 5,10b-ethanophenanthridine nucleus (crinine-type). Furthermore, the antimicrobial activity of the chloroform extract of the flowers of c. nobilis along with some of the isolated alkaloids has been studied.