N-oxide alkaloids from Crinum amabile (Amaryllidaceae)

Abstract

Natural products play an important role in the development of new drugs. In this context, the Amaryllidaceae alkaloids have attracted considerable attention in view of their unique structural features and various biological activities. In this study, twenty-three alkaloids were identified from Crinum amabile by GC-MS and two new structures (augustine N-oxide and buphanisine N-oxide) were structurally elucidated by NMR. Anti-parasitic and cholinesterase (AChE and BuChE) inhibitory activities of six alkaloids isolated from this species, including the two new compounds, are described herein. None of the alkaloids isolated from C. amabile gave better results than the reference drugs, so it was possible to conclude that the N-oxide group does not increase their therapeutic potential.

Biosynthesis and Biological Activities of Newly Discovered Amaryllidaceae Alkaloids

“…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.…”

“…Two new AAs, 6-O-demethylbelladine (1) and 4 -O-demethylbelladine (2), belonging to the norbelladine-type, together with twenty known alkaloids, were isolated from fresh bulbs of Nerine bowdenii by standard chromatographic methods [60]. From the organic extract of N. sarniensis, an indigenous South African Amaryllidaceae, were isolated two new alkaloids named sarniensinol (77) and sarniensine (78) belonging to the mesembrine group, and a new crinine-type alkaloid named crinsarnine (43), together with bowdensine, tazettine, 3-epimacronine, lycorine, 1-O-acetyl-lycorine, and hippadine. Sarniensinol (77), sarniensine (78), and crinsarnine (43) were characterized by extensive spectroscopic and chiroptical methods [78,86].…”

The Bioassay-Guided Fractionation and Identification of Potent Acetylcholinesterase Inhibitors from Narcissus c.v. ‘Hawera’ Using Optimized Vacuum Liquid Chromatography, High Resolution Mass Spectrometry and Bioautography

“…Three plates from three experiments were obtained showing the separation of the analyzed fractions, which allowed us to detect the most active AChE inhibitors. The deep purple background of the plate was obtained as a consequence of the reaction of 2-naphtol with Fast Blue B Salt reagent, and white spots indicated the presence of AChE inhibitors, which are stable for a long time [ 20 , 21 ]. Strong enzymatic activity represented as white spots on a purple background can be seen especially in the second and third experiments (videosan B–C are presented in Figure 3 ).…”

“…This allowed us to shorten the duration of the analysis, by omitting some of processes like centrifugation and distillation. Only few published papers dealt with the application of VLC in separation of the Amaryllidaceae alkaloids [ 20 , 21 , 30 ], and only silica as the stationary phase was used. VLC was also a part of combined chromatographic methods, including also PLC and GC/MS.…”

“…Knowing possible advantages of VLC in a rapid separation and fractionation of natural compounds we decided to develop bioassay guided fractionation of the alkaloids from the bulbs of Narcissus triandrus L. c.v. ‘Hawera’ using an optimized and a novel gradient VLC approach and find the best experimental conditions for an efficient isolation of alkaloids with strong anti-AChE activity. To date, only few papers on VLC isolation of Amaryllidaceae alkaloids have been published [ 20 , 21 ], but none of them described comprehensive combination of PLC, gradient VLC, TLC-bioautography and HPLC/ESI-QTOF-MS for rapid screening and fractionation of the bioactive Amaryllidaceae alkaloids. Bioassay-guided isolation of bioactive compound is a modern and efficient technique in metabolites screening.…”