Cytotoxicity of Naturally Occurring Isoquinoline Alkaloids of Different Structural Types.

Forty-six isoquinoline alkaloids, of eleven structural types isolated in our laboratory, have been evaluated for their cytotoxicity against two cancer cell lines (Caco-2 and Hep-G2 cancer cells), as well as against normal human lung fibroblast cells. Only scoulerine, aromoline, berbamine and parfumidine showed significant cytotoxic effects, but only scoulerine was active against both Caco-2 and Hep-G2 cells (IC50 values 6.44 ± 0.87 and 4.57 ± 0.42, respectively). Unfortunately, except for parfumidine, the other active alkaloids were also cytotoxic to the normal human lung fibroblast cells.

Isoquinoline Alkaloids from Fumaria officinalis L. and Their Biological Activities Related to Alzheimer's Disease.

Two new isoquinoline alkaloids, named fumaranine (2) and fumarostrejdine (10), along with 18 known alkaloids were isolated from aerial parts of Fumaria officinalis. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses and by comparison with literature data. The absolute configuration of the new compound 2 was determined by comparing its circular dichroism spectra with those of known analogs. Compounds isolated in sufficient amounts were evaluated for their acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase (POP), and glycogen synthase kinase-3ß inhibitory activities. Parfumidine (8) and sinactine (15) exhibited potent POP inhibition activities (IC50 99±5 and 53±2 µM, resp.).

(+)-Chenabinol (Revised NMR Data) and Two New Alkaloids from Berberis vulgaris and their Biological Activity.

A known alkaloid (+)-chenabinol (1) and two new secobisbenzylisoquinoline alkaloids were isolated by standard chromatographic methods from the root bark of Berberis vulgaris L. The structures of the new alkaloids, named berkristine (2) and verfilline (3), were established by spectroscopic (including 2D NMR), and HRMS (ESI) methods. The alkaloids were tested for their inhibition activity of human cholinesterases and prolyl oligopeptidase. Compound 1 inhibited human butyrylcholinesterase with an IC50 value of 44.8 ± 5.4 µM.

In Vitro Inhibitory Effects of 8-O-Demethylmaritidine and Undulatine on Acetylcholinesterase and Their Predicted Penetration across the Blood-Brain Barrier.

Alzheimer's disease is the most common cause of dementia. Currently, acetylcholinesterase (AChE) inhibition is the most widely used therapeutic treatment. A large number of naturally occurring compounds have been found to inhibit AChE. In this report the mechanism of AChE inhibition of two Amaryllidaceae alkaloids, 8-O-demethylmaritidine (1) and undulatine (2), and their possible penetration across the blood-brain barrier have been studied. Both compounds act via a mixed inhibition mechanism. Based on the parallel artificial permeation assay (PAMPA) for the prediction of blood-brain barrier (BBB) penetration, only 2 should be able to cross the BBB by passive permeation.

Alkaloids from Peumus boldus and their acetylcholinesterase, butyrylcholinesterase and prolyl oligopeptidase inhibition activity.

Eleven isoquinoline alkaloids (1-11) were isolated from dried leaves of Peumus boldus Mol. by standard chromatographic methods. The chemical structures were elucidated by MS, and 1D and 2D NMR spectroscopic analysis, and by comparison with literature data. Compounds isolated in sufficient amount 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. Promising butyrylcholinesterase inhibition activities were demonstrated by two benzylisoquinoline alkaloids, reticuline (8) and N-methylcoclaurine (9), with IC50 values of 33.6 ± 3.0 µM and 15.0 ± 1.4 µM, respectively. Important prolyl oligopeptidase inhibition activities were shown by N-methyllaurotetanine (6) and sinoacutine (4) with IC50 values of 135.4 ± 23.2 µM and 143.1 ± 25.4 µM, respectively. Other tested compounds were considered inactive.

Antimicrobial activity of extracts and isoquinoline alkaloids of selected papaveraceae plants.

Alkaloidal extracts of seven selected plants of the family Papaveraceae were studied with respect to their activity against six strains of pathogenic bacteria and their alkaloidal fingerprint. Twenty-four alkaloids were determined by GC/MS, and twenty of them identified from their mass spectra, retention times and retention indexes. In the antibacterial assay, three Gram-positive (Enterorococcus faecalis, Staphylococcus aureus and S. hyicus), and three Gram-negative (Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa) strains were used. The most promising antimicrobial activity was shown by the alkaloidal extract of Macleaya cordata with MIC values of 16 µg/mL for Staphylococcus aureus, 32 µg/mL for Enterococcus faecalis and 64 µg/mL for Staphylococcus hyicus and Escherichia coli. All the tested pure isoquinoline alkaloids were considered inactive within the tested concentrations.

Berbanine: a new isoquinoline-isoquinolone alkaloid from Berberis vulgaris (Berberidaceae).

A new isoquinoline-isoquinolone alkaloid was isolated from the root bark of Berberis vulgaris and named berbanine. The structure was established by spectroscopic methods (including 2D NMR, HR-EI-MS).

Identification of pavinane alkaloids in the genera Argemone and Eschscholzia by GC-MS.

The genera Eschscholtzia and Argemone (Papaveraceae) represent a rich source of pavinane alkaloids, the identification of which in alkaloid extracts is generally problematic without standards. The alkaloid extracts of three Argemone and four Eschscholtzia species were analyzed using GC-MS. The alkaloids were identified based on comparison of their mass spectra with commercial libraries, with reported data in the literature and with spectra of reference compounds. A total of 23 alkaloids of six structural types (pavinane, protopine, benzylisoquinoline, benzophenanthridine, aporphine and protoberberine) were identified. The fragmentation pathway of pavinane alkaloids was used for their identification. O-Methylneocaryachine has been reported for the first time from a natural sources and the alkaloid pattern of Eschscholzia pulchella has been analyzed and described for the first time.

Ecdysterone and its activity on some degenerative diseases.

Beside ecdysone (1), ecdysterone (2) is one of the most common 5beta-cholest-7-en-6-one (ecdysteroid) derivatives, which, besides having a hormonal effect on invertebrates, possesses a number of favorable non-hormonal biological effects on mammals. The most interesting of these is that on degenerative diseases, one of which, up to now not clarified in detail, is the so-called adaptogenic effect (protection of the organism against adverse stress factors) associated with anabolic, gastroprotective, and antioxidant effects. A second group of favorable effects is the possibility of suppression of neurodegenerative processes and protection of the cardiovascular system (metabolic syndrome symptom suppression, antidiabetic activity, and protection of heart and blood vessels). Because of these properties, ecdysterone has the potential to be developed as a medicinal agent.

Isolation and cholinesterase activity of Amaryllidaceae alkaloids from Nerine bowdenii.

Amaryllidaceae species are known as ornamental plants. Some contain galanthamine, an acetylcholinesterase inhibitor. The chemical composition of the alkaloid extract of bulbs of Nerine bowdenii Watson has been analyzed by means of GC/MS. Twenty-two compounds were detected and nineteen of them identified, one of which was belladine. The alkaloid extract showed promising cholinesterase inhibitory activities against human blood acetylcholinesterase (HuAChE; IC50 = 87.9 +/- 3.5 microg/mL) and human plasma butyrylcholinesterase (HuBuChE; IC50 = 14.8 +/- 1.1 microg/mL). Belladine inhibited HuAChE and HuBuChE in a dose-dependent manner with IC50 values of 781 +/- 12.5 microM and 284.8 +/-4.2 microM, respectively.