Amaryllidaceae Alkaloids of Different Structural Types from Narcissus L. cv. Professor Einstein and Their Cytotoxic Activity

Abstract

In this detailed phytochemical study of Narcissus cv. Professor Einstein, we isolated 23 previously known Amaryllidaceae alkaloids (1–23) of several structural types and one previously undescribed alkaloid, 7-oxonorpluviine. The chemical structures were identified by various spectroscopic methods (GC-MS, LC-MS, 1D, and 2D NMR spectroscopy) and were compared with literature data. Alkaloids which had not previously been isolated and studied for cytotoxicity before and which were obtained in sufficient amounts were assayed for their cytotoxic activity on a panel of human cancer cell lines of different histotype. Above that, MRC-5 human fibroblasts were used as a control noncancerous cell line to determine the general toxicity of the tested compounds. The cytotoxicity of the tested alkaloids was evaluated using the WST-1 metabolic activity assay. The growth of all studied cancer cell lines was inhibited by pancracine (montanine-type alkaloid), with IC50 values which were in the range of 2.20 to 5.15 µM.

Biosynthesis and Biological Activities of Newly Discovered Amaryllidaceae Alkaloids

“…The anti-inflammatory activity of galantamine-, plicamin-and seco-plicamin-type (11−16, 56-67 and 68-69) was evaluated in vitro by studying the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 mouse macrophages. Among the tested compounds, two plicamine-type alkaloids (59) and 60 Moreover, (73) and (74) displayed highest antibacterial activity with IC 50 values < 0.50 mM, while (71) and (72) had weak activity [84].…”

“…Several of these novel AAs belong to known structural types, while others harbor new structures. The 91 AAs were classified in this manuscript as I) norbelladine-type (1-6), II) cherylline-type (7, 8), III) galantamine-type (9-16), IV) lycorine-type (17-25), V) homolycorine-type (26)(27)(28)(29)(30), VI) crinine-type (31-50), VII) narciclasine-type (51), VIII) pretazettine-type (52-54), IX) montanine-type (55), and X) other types including AAs related to plicamine (56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67), seco-plicamine (68-70), cripowellin (71)(72)(73)(74)(75)(76), mesembrine (77,78), and various others AAs (79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91). Structures of novel AAs belonging to the I to III scaffold types (norbelladine-, cherylline-, and galantamine-type) are depicted in Figure 3, whereas types IV and V (lycorine-and homolycorine-type) are represented in Figure 4.…”

“…Furthermore, it has been demonstrated that the presence of the unaltered diol functionality in the C-ring in its original configuration in lycorine series, the stereochemistry of the C/D ring junction and the conformational freedom of the C-ring were required for the anticancer activity [96] [88]. Cripowellin-form (71)(72)(73)(74)(75)(76) and Zephycandidine A (81) belonging to the other-type of AA may be potential targets for further anticancer investigations.…”

“…7-Oxonorpluviine ( 24 ), a lycorine-type alkaloid was isolated from fresh bulbs of Narcissus L. cv. Professor Einstein, together with twenty three known AAs, and their structures were identified by using various spectroscopic methods like (GC-MS, LC-MS, 1D, and 2D NMR spectroscopy) [ 71 ]. Pseudolycorine N -oxide ( 25 ) was isolated from Narcissus tazetta whole plant, and the structural elucidation was determined by spectroscopic data analysis [ 72 ].…”

Cytotoxic Agents in the Minor Alkaloid Groups of the Amaryllidaceae

“…Analysis of fresh bulb extracts led to the identification of 22 alkaloids, one of which was the planar, tricyclic compound trisphaeridine (8) [19]. The cytotoxicity component of the investigation used SH-SY5Y neuroblastoma cells that were exposed to trisphaeridine (at 6.25, 12.5, 25, 50, and 100 µM) as well as to the cell perturbation agents H 2 O 2 (300 µM), Aβ [25][26][27][28][29][30][31][32][33][34][35] (1 µM), or CoCl 2 (265 µM) [19]. Significant relief from H 2 O 2 -, Aβ 25-35 -and CoCl 2induced injuries was observed for trisphaeridine at 12.5 µM relative to untreated cells [19].…”