Bioactive alkaloids from Brunsvigia radulosa

doi:10.1016/S0031-9422(99)00575-0

Phytochemistry

Volume 53, Issue 5, 1 March 2000, Pages 587-591

https://doi.org/10.1016/S0031-9422(99)00575-0 Get rights and content

Abstract

A phytochemical investigation of the bulbs of Brunsvigia radulosa yielded the new alkaloid 1-O-acetylnorpluviine, together with the known structures 1-epideacetylbowdensine, crinamine, crinine, hamayne, lycorine, anhydrolycorin-6-one and sternbergine. All structures were established by spectroscopic evidence. Some of the $^{13} C$ assignments which were reported for crinamine and hamayne were corrected by means of 2D NMR techniques. In order to provide a further structure for biological testing, crinamine was converted to apohaemanthamine. The alkaloids were tested for activity against two strains of cultured Plasmodium falciparum and for cytotoxicity with BL6 mouse melanoma cells.

Introduction

The genus Brunsvigia, subtribe Amaryllidinae, tribe Amaryllideae (Amaryllidaceae), is widely distributed over both summer- and winter- rainfall regions of the southern and southwestern regions of South Africa. Several Amaryllideae species have been used in the traditional medicine of the indigenous peoples of the country (Hutchings, Scott, Lewis & Cunningham, 1996). In a continuation of our phytochemical studies on genera from the subtribes Amaryllidinae and Crininae (Viladomat, Bastida, Codina, Nair & Campbell, 1997), we have investigated the taxon Brunsvigia radulosa Herb. The choice of this species was prompted by a report of the inhibitory activity of an extract of the plant against P 388 lymphocytic leukaemia in mice (Charlson, 1980), and by our own observation of moderate activity against two strains of Plasmodium falciparum. In the present study we describe the isolation and characterisation of the novel alkaloid 1-O-acetylnorpluviine (1), together with the known structures, 1-epideacetylbowdensine, crinamine, crinine, hamayne, lycorine, anhydrolycorin-6-one (2) and sternbergine. In addition, in order to provide a further structure for our studies on the antiplasmodial and cytotoxic activity of Amaryllidaceae alkaloids, crinamine was converted to the C-3/C-11 epoxide, apohaemanthamine (3).

Section snippets

Results and discussion

The alkaloids were isolated from an ethanol extract of the fresh bulbs of Brunsvigia radulosa. 1-O-acetylnorpluviine (1) gave a M⁺ ion at 315.1465 in the high resolution EI mass spectrum, which corresponded with a molecular formula, C₁₈H₂₁NO₄. The mass spectrum and the $^{1} H$ -NMR spectrum showed structural features similar to those of the known pyrrolo[de]phenanthridine alkaloid, 1-O-acetylcaranine (Pettit, Gaddamidi, Goswami & Cragg, 1984). The four singlets at $δ$ 6.74, 6.64, 3.83, and 1.90 in the $^{1}$

General

Mps are uncorr. IR spectra were recorded in KBr discs. EIMS were obtained at 70 eV. NMR spectra were measured using Varian VXR 400 and VXR 500 instruments, in the solvents specified and with TMS as int. standard. Chemical shifts are reported in $δ$ units (ppm) and coupling constants (J) in Hz. Silica gel 60 F₂₅₄ (Merck) was used for analytical (0.25 mm) TLC and flash cc was carried out on Silica gel N for thin layer chromatography (Macherey Nagel). Spots on chromatograms were detected under UV

Acknowledgements

Financial support from the Medical Research Council and the University of Cape Town is gratefully acknowledged. We also thank Dr J. du Preez from the Department of Nature Conservation, Bloemfontein, for the collection and authentication of the plant material.

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A new alkaloid from Pancratium maritimum - Structure elucidation using computer-assisted structure elucidation (CASE) and evaluation of cytotoxicity and anti-SARS-CoV-2 activity
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Pancratium maritimum L. (or ‘sea daffodil’) is one of the most studied plant species in the Amaryllidaceae family. Recently, due to the advancement of new probabilistic methods and spectroscopic techniques, the potential for phytochemical investigations on isomeric compounds has significantly improved. In this study, application of these techniques in combination with conventional phytochemical analysis led to the isolation and identification of a new alkaloid named 2β,10bα-dihydroxy-9-O-demethylhomolycorine from P. maritimum, together with 17 known ones. Assessment of anti-SARS-CoV-2 activity and cytotoxicity on a Vero E6 cell line for all compounds revealed four compounds with weak anti-SARS-CoV-2 potency at non-cytotoxic concentrations, namely of 9-O-demethylhomolycorine (EC₅₀ = 44 µM), galanthamine (EC₅₀ = 70 µM), 1-O-acetyl-norpluviine (EC₅₀ = 80 µM) and 1-O-acetyl-10-O-methylpseudolycorine (EC₅₀ = 47 µM). On the other hand, cytotoxicity was observed for 2β,10bα-dihydroxy-9-O-demethylhomolycorine (CC₅₀ = 13.28 µM), haemanthamine (CC₅₀ = 0.76 µM), 6α- and 6β-haemanthidine (CC₅₀ = 5.43 µM), 11-hydroxyvittatine (CC₅₀ = 10.57 µM) and pseudolycorine (CC₅₀ = 3.41 µM).
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^☆: Part 7 in the series “Alkaloids from South African Amaryllidaceae”. For part 6 see Nair et al., 1998. [Nair, J.J., Campbell, W.E., Gammon, D.W., Albrecht, C.F., Viladomat, F., Codina, C. & Bastida, J. (1998). Phytochemistry, 49, 2539].

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Phytochemistry

Abstract

Introduction

Section snippets

Results and discussion

General

Acknowledgements

References (13)

Antineoplastic constituents of some southern african plants

J. Ethnopharmacol

Alkaloids from Brunsvigia josephinae

Phytochemistry

Composition and antimalarial activity in vitro of Tetradenia riparia

Planta Med

Cytotoxic and antimalarial alkaloids from Brunsvigia littoralis

Planta Med

Alkaloids of the amaryllidaceae. Part XIII: The structure of haemanthamine and crinamine

J. Amer. Chem. Soc

Carbon-13 nuclear magnetic resonance spectra of Amaryllidaceae alkaloids. Part I: Alkaloids with the crinane skeleton

Mag. Res. Chem

Cited by (76)

Amaryllidaceae alkaloids from the bulbs of Crinum latifolium L. and their cholinesterase inhibitory activities

A new alkaloid from Pancratium maritimum - Structure elucidation using computer-assisted structure elucidation (CASE) and evaluation of cytotoxicity and anti-SARS-CoV-2 activity

Structurally diverse alkaloids with nine frameworks from Zephyranthes candida and their acetylcholinesterase inhibitory and anti-inflammatory activities

Alkaloids with cholinesterase inhibitory activities from the bulbs of Crinum × amabile Donn ex Ker Gawl

Isolation of the antibacterial alkaloid distichamine from Crossyne Salisb. (Amaryllidaceae: Amaryllideae: Strumariinae)

Recent Applications of Selected Name Reactions in the Total Synthesis of Alkaloids

Bioactive alkaloids from Brunsvigia radulosa☆

Abstract

Introduction

Section snippets

Results and discussion

General

Acknowledgements

J. Ethnopharmacol

Phytochemistry

Composition and antimalarial activity in vitro of Tetradenia riparia

Planta Med

Cytotoxic and antimalarial alkaloids from Brunsvigia littoralis

Planta Med

Alkaloids of the amaryllidaceae. Part XIII: The structure of haemanthamine and crinamine

J. Amer. Chem. Soc

Carbon-13 nuclear magnetic resonance spectra of Amaryllidaceae alkaloids. Part I: Alkaloids with the crinane skeleton

Mag. Res. Chem