Thalifaberidine, a Cytotoxic Aporphine-Benzylisoquinoline Alkaloid from Thalictrum faberi

Abstract

From Thalictrum faberi, thalifaberidine [1], a new aporphine-benzylisoquinoline alkaloid, together with four known alkaloids, thalifaramine [2], thalifaricine [3], thalifarazine [4], and thalifaronine [5], were isolated. Thalifaberidine [1] was identified as 6',8-desmethylthalifaberine, and its 1H- and 13C-nmr data were completely assigned through the use of one- and two-dimensional nmr techniques. Thalifaberidine [1], thalifaberine [6], and thalifasine [7] showed cytotoxic activity against several human cancer cell lines, as well as antimalarial activity.

Electrospray Tandem Mass Spectrometry for Structural Characterization of Aporphine-Benzylisoquinoline Alkaloids

“…In the Q1 scan MS data, all the alkaloids revealed apparent protonated molecules (MH + ions) or molecular ion (M +• ) (dimethothalicarpine), together with an intense doublyprotonated molecule (MH 2+ ion) (base peak) except thaliadine, a benzaldehyde-aporphine ether. These data were not observed for those in the EI-MS, CI-MS and FAB-MS. [1][2][3][8][9][10][11][12][13][14][15][16][17][18][19][20] In the electrospray MS/MS, the bond-cleavage at the benzylic ring AB and ring E formed abundant ethereal aporphinebenzylic ions, which are similar fragment patterns to those in the EI-MS data; however, those fragment ions are not observed or show in very low abundances in both CI-MS and FAB-MS. The fragment ion corresponding to ring E, such as fragment ion, dimethoxybenzylic ion, e, is less abundant in the MS/MS data of the investigated alkaloids due to less ionic property and less proton affinities.…”

“…[1][2][3] Aporphine-benzylisoquinoline and bisbenzylisoquinoline alkaloids, two important dimeric classes of isoquinoline alkaloids, exert antihypertensive, antiarrhythmogenic, antianginal, antimicrobial, analgesic, neuromuscular blocking, muscle relaxant and antitumor activities. [1][2][3][4][5][6][7][8][9][10] Thalicarpine, northalicarpine, thalmelatine, adiantifoline and thalirevolutine, five of the ten investigated aporphinebenzylisoquinoline alkaloids exhibit antimicrobial, antitumor and hypotensive activities. [1][2][3][4][5][6][7][8][9][10] Previously, structural elucidation of these natural products has mainly relied on the ultraviolet (UV), infrared (IR), nuclear magnetic reso-nance (NMR), mass spectrometry (MS) [electron ionization (EI), chemical ionization (CI), fast atom bombardment (FAB)] and circular dichroism (CD) spectroscopic data, derivatization, chemical degradation and total synthesis.…”

“…[1][2][3]6,[8][9][10][11][12][13][14][15][16][17][18][19][20] Early EI-MS studies of aporphine-benzylisoquinoline alkaloids displayed low abundances of molecular ions (M +• : < 1% relative abundance) for the secondary and tertiary alkaloids and less fragment ions in high abundance. [1][2][3][6][7][8][9][10][11][12][13][14][15][16][17][18] The CI-MS and FAB-MS spectra showed apparent protonated molecules (MH + ions) for these secondary and tertiary alkaloids; however, there were either no or weak molecular ions for the quaternary alkaloids observed and less fragment ions for structural information of these alkaloids. We have reported previously preliminary results for the structural elucidation of ten aporphine-benzylisoquinoline alkaloids using electrospray MS and tandem (MS/MS) techniques 21 and have also published the in vitro metabolism of thalicarpine, an antitumor, antimicrobial and hypotensive alkaloid, using the rat hepatic S9 incubation.…”

Green Routes for the Production of Enantiopure Benzylisoquinoline Alkaloids

“…The interest in the wide variety of BIA structures is paramount, due to their well-established and long-standing pharmacological profiles [ 2 ]. The most covered therapeutic areas by BIAs are analgesics [ 3 , 4 ], antimicrobial [ 5 ], antimalarial [ 6 , 7 ], anti-HIV [ 7 , 8 , 9 ], and anticancer agents [ 10 , 11 , 12 ], whereas new areas are being explored more recently for BIAs, such as their employment as cholesterol-lowering and protecting agents against the atherosclerotic disease [ 13 , 14 , 15 , 16 ] and as signaling suppressors in colon cancer cells [ 17 ].…”

Apoptosis of Human Highly Metastatic Lung Cancer Cell Line 95-D Induced by Acutiaporberine, a Novel Bisalkaloid Derived from Thalictrum acutifolium

“…Many species of the genus Thalictrum are often used in anti-inflammation, anti-virus, antibacterial, antitumor and hypertension treatments. They contain various kinds of bioactive components that show antirumor activities both in vitro [6], [7], [8] and in vivo [9], [10], [11].…”