Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As bleeding was suggested to be a side effect of the isoquinoline alkaloid berberine, we decided to ascertain if different isoquinoline alkaloids could influence hemocoagulation through the inhibition of either platelet aggregation or blood coagulation. Initially, a total of 14 compounds were screened for antiplatelet activity in whole human blood by impedance aggregometry. Eight of them demonstrated an antiplatelet effect against arachidonic acid-induced aggregation. Papaverine and bulbocapnine were the most potent compounds with biologically relevant IC50 values of 26.9 ± 12.2 μM and 30.7 ± 5.4 μM, respectively. Further testing with the same approach confirmed their antiplatelet effects by employing the most physiologically relevant inducer of platelet aggregation, collagen, and demonstrated that bulbocapnine acted at the level of thromboxane receptors. None of the alkaloids tested had an effect on blood coagulation measured by a mechanical coagulometer. In conclusion, the observed antiplatelet effects of isoquinoline alkaloids were found mostly at quite high concentrations, which means that their clinical impact is most likely low. Bulbocapnine was an exception. It proved to be a promising antiplatelet molecule, which may have biologically relevant effects.

• Klíčová slova
• antiplatelet, bleeding, bulbocapnine, drug, isoquinoline,
• MeSH
• agregace trombocytů * MeSH
• alkaloidy * farmakologie   MeSH
• inhibitory agregace trombocytů farmakologie   MeSH
• isochinoliny farmakologie   MeSH
• lidé MeSH
• trombocyty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkaloidy * MeSH
• inhibitory agregace trombocytů MeSH
• isochinoliny MeSH

Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyses proline-containing peptides at the carboxy terminus of proline residues. It has been associated with schizophrenia, bipolar affective disorder, and related neuropsychiatric disorders and therefore may have important clinical implications. Thirty-one isoquinoline alkaloids of various structural types, previously isolated in our laboratory, were screened for their ability to inhibit prolyl oligopeptidase. Promising results have been showed by alkaloids californidine (IC50=55.6±3.5 μM), dihydrosanquinarine (IC50=99.1±7.6 μM), corypalmine (IC50=128.0±10.5 μM) and N-methyllaurotetanine (IC50=135.0±11.7 μM).

• Klíčová slova
• Argemonine (CID: 442168), Berberine (PubChem CID: 2353), Californidine, Californidine (PubChem CID: 45266443), Canadine (PubChem CID: 443422), Corynoline (PubChem CID: 177014), Corypalmine (PubChem CID: 185605), Dihydrosanquinarine, Dihydrosanquinarine (PubChem CID: 124069), Isoquinoline alkaloids, N-Methyllaurotetanine (PubChem CID: 16573), Prolyl oligopeptidase,
• MeSH
• alkaloidy chemie   MeSH
• aporfiny chemie   MeSH
• dioxoly chemie   MeSH
• heterocyklické sloučeniny tetra- a více cyklické chemie   MeSH
• inhibitory serinových proteinas chemie   MeSH
• isochinoliny chemie   MeSH
• molekulární struktura MeSH
• prolyloligopeptidasy MeSH
• serinové endopeptidasy chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkaloidy MeSH
• aporfiny MeSH
• californidine MeSH Prohlížeč
• corypalmine MeSH Prohlížeč
• dioxoly MeSH
• heterocyklické sloučeniny tetra- a více cyklické MeSH
• inhibitory serinových proteinas MeSH
• isochinoliny MeSH
• N-methyllaurotetanine MeSH Prohlížeč
• prolyloligopeptidasy MeSH
• serinové endopeptidasy MeSH

Common procedure of isolation of isoquinoline alkaloids and the novel separation techniques are discussed and exemplified. The methods used for determination of isoquinoline alkaloids are reviewed, including GC, HPLC, TLC, immunochemical methods and some special techniques. The selected examples of applications are included.

• MeSH
• alkaloidy analýza   izolace a purifikace   MeSH
• chromatografie metody   MeSH
• isochinoliny analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• alkaloidy MeSH
• isochinoliny MeSH

AKR1C3 is an important human enzyme that participates in the reduction of steroids and prostaglandins, which leads to proliferative signalling. In addition, this enzyme also participates in the biotransformation of xenobiotics, such as drugs and procarcinogens. AKR1C3 is involved in the development of both hormone-dependent and hormone-independent cancers and was recently demonstrated to confer cell resistance to anthracyclines. Because AKR1C3 is frequently upregulated in various cancers, this enzyme has been suggested as a therapeutic target for the treatment of these pathological conditions. In this study, nineteen isoquinoline alkaloids were examined for their ability to inhibit a recombinant AKR1C3 enzyme. As a result, stylopine was demonstrated to be the most potent inhibitor among the tested compounds and exhibited moderate selectivity towards AKR1C3. In the follow-up cellular studies, stylopine significantly inhibited the AKR1C3-mediated reduction of daunorubicin in intact cells without considerable cytotoxic effects. This inhibitor could therefore be used as a model AKR1C3 inhibitor in research or evaluated as a possible therapeutic anticancer drug. Furthermore, based on our results, stylopine can serve as a model compound for the design and future development of structurally related AKR1C3 inhibitors.

• Klíčová slova
• AKR1C3, Alkaloids, Cancer, Inhibitor, Isoquinoline, Natural,
• MeSH
• 3-hydroxysteroid dehydrogenasy antagonisté a inhibitory   MeSH
• berberinové alkaloidy farmakologie   MeSH
• hydroxyprostaglandindehydrogenasy antagonisté a inhibitory   MeSH
• inhibitory enzymů farmakologie   MeSH
• kolorektální nádory farmakoterapie   enzymologie   patologie   MeSH
• lidé MeSH
• nádorové buňky kultivované MeSH
• nádory prsu farmakoterapie   enzymologie   patologie   MeSH
• proliferace buněk MeSH
• protein AKR1C3 MeSH
• testosteron metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-hydroxysteroid dehydrogenasy MeSH
• AKR1C3 protein, human MeSH Prohlížeč
• berberinové alkaloidy MeSH
• hydroxyprostaglandindehydrogenasy MeSH
• inhibitory enzymů MeSH
• protein AKR1C3 MeSH
• stylopine MeSH Prohlížeč
• testosteron MeSH

Six different isoquinoline alkaloids (sanguinarine, chelerythrine, berberine, coptisine, allocryptopine, and protopine) were extracted by butanol and octanol from aqueous solution, pH 4.5. The samples were analyzed by HPLC. Butanol extraction was non-selective, alkaloids passed into organic phase in 83-98%. Octanol extraction provided more selective yields: sanguinarine 99%, chelerythrine 94%, berberine 18%, coptisine 16%, allocryptopine 7.5%, protopine 7%. Further, we tested octanol treatment of extract from Dicranostigma lactucoides. The octanol extraction yields were also selective: sanguinarine 98%, chelerythrine 92%, chelirubine 92.5%, protopine 6% and allocryptopine 3.5%. 6-Butoxy-5,6-dihydrosanguinarine and 6-butoxy-5,6-dihydrochelerythrine were prepared and their NMR and MS data are reported and discussed.

• MeSH
• benzofenantridiny izolace a purifikace   MeSH
• butanoly chemie   MeSH
• isochinoliny izolace a purifikace   MeSH
• oktanoly chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzofenantridiny MeSH
• butanoly MeSH
• isochinoliny MeSH
• oktanoly MeSH

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-3β inhibitory activities. Parfumidine (8) and sinactine (15) exhibited potent POP inhibition activities (IC50 99±5 and 53±2 μM, resp.).

• Klíčová slova
• Acetylcholinesterase, Butyrylcholinesterase, Fumaria officinalis, Glycogen synthase kinase-3β, Isoquinoline alkaloids, Prolyl oligopeptidase,
• MeSH
• acetylcholinesterasa metabolismus   MeSH
• alkaloidy chemie   izolace a purifikace   farmakologie   MeSH
• Alzheimerova nemoc farmakoterapie   enzymologie   MeSH
• butyrylcholinesterasa metabolismus   MeSH
• Fumaria chemie   MeSH
• inhibitory enzymů chemie   izolace a purifikace   farmakologie   MeSH
• isochinoliny chemie   izolace a purifikace   farmakologie   MeSH
• kinasa 3 glykogensynthasy antagonisté a inhibitory   metabolismus   MeSH
• kinasa glykogensynthasy 3beta MeSH
• lidé MeSH
• molekulární struktura MeSH
• prolyloligopeptidasy MeSH
• serinové endopeptidasy metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• alkaloidy MeSH
• butyrylcholinesterasa MeSH
• fumaranine MeSH Prohlížeč
• fumarostrejdine MeSH Prohlížeč
• GSK3B protein, human MeSH Prohlížeč
• inhibitory enzymů MeSH
• isochinoliny MeSH
• kinasa 3 glykogensynthasy MeSH
• kinasa glykogensynthasy 3beta MeSH
• PREPL protein, human MeSH Prohlížeč
• prolyloligopeptidasy MeSH
• serinové endopeptidasy MeSH

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).

• MeSH
• alkaloidy izolace a purifikace   MeSH
• Berberis chemie   MeSH
• isochinoliny chemie   izolace a purifikace   MeSH
• kořeny rostlin chemie   MeSH
• magnetická rezonanční spektroskopie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkaloidy MeSH
• berbanine MeSH Prohlížeč
• isochinoliny MeSH

Voltage-gated Na+ (NaV) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel NaV channel ligands. With the objective of discovering new blockers of NaV channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of NaV channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC50. These five alkaloids were then assayed using the Na+ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNaV1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na+ currents elicited by the hNaV1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na+ currents elicited by the hNav1.2 and hNav1.6 channels, with IC50 values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block NaV channels, with promising therapeutical applications.

• Klíčová slova
• GH3b6 cells, Na+ fluorescent probe ANG-2, isoquinoline alkaloids, oxoaporphine, voltage sensor probes, voltage-gated sodium channel,
• MeSH
• alkaloidy * farmakologie   MeSH
• batrachotoxiny metabolismus   farmakologie   MeSH
• fluorescenční barviva * MeSH
• HEK293 buňky MeSH
• isochinoliny farmakologie   MeSH
• lidé MeSH
• ligandy MeSH
• sodík metabolismus   MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaloidy * MeSH
• batrachotoxiny MeSH
• fluorescenční barviva * MeSH
• isochinoliny MeSH
• ligandy MeSH
• sodík MeSH

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease recognized as the most common form of dementia among elderly people. Due to the fact that the exact pathogenesis of AD still remains to be fully elucidated, the treatment is only symptomatic and available drugs are not able to modify AD progression. Considering the increase in life expectancy worldwide, AD rates are predicted to increase enormously, and thus the search for new AD drugs is urgently needed. Due to their complex nitrogen-containing structures, alkaloids are considered to be promising candidates for use in the treatment of AD. Since the introduction of galanthamine as an antidementia drug in 2001, Amaryllidaceae alkaloids (AAs) and further isoquinoline alkaloids (IAs) have been one of the most studied groups of alkaloids. In the last few years, several compounds of new structure types have been isolated and evaluated for their biological activity connected with AD. The present review aims to comprehensively summarize recent progress on AAs and IAs since 2010 up to June 2021 as potential drugs for the treatment of AD.

• Klíčová slova
• Alzheimer’s disease, acetylcholinesterase, butyrylcholinesterase, docking study, isoquinoline alkaloids, monoaminooxidase, neuroprotective activity, prolyl oligopeptidase,
• MeSH
• alkaloidy amarylkovitých metabolismus   MeSH
• Alzheimerova nemoc metabolismus   MeSH
• Amaryllidaceae chemie   MeSH
• neurodegenerativní nemoci metabolismus   MeSH
• prolyloligopeptidasy metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• alkaloidy amarylkovitých MeSH
• prolyloligopeptidasy MeSH

Data on alkaloid interactions with the physiologically important transition metals, iron and copper, are mostly lacking in the literature. However, these interactions can have important consequences in the treatment of both Alzheimer's disease and cancer. As isoquinoline alkaloids include galanthamine, an approved drug for Alzheimer's disease, as well as some potentially useful compounds with cytostatic potential, 28 members from this category of alkaloids were selected for a complex screening of interactions with iron and copper at four pathophysiologically relevant pH and in non-buffered conditions (dimethyl sulfoxide) by spectrophotometric methods in vitro. With the exception of the salts, all the alkaloids were able to chelate ferrous and ferric ions in non-buffered conditions, but only five of them (galanthine, glaucine, corydine, corydaline and tetrahydropalmatine) evoked some significant chelation at pH 7.5 and only the first two were also active at pH 6.8. By contrast, none of the tested alkaloids chelated cuprous or cupric ions. All the alkaloids, with the exception of the protopines, significantly reduced the ferric and cupric ions, with stronger effects on the latter. These effects were mostly dependent on the number of free aromatic hydroxyls, but not other hydroxyl groups. The most potent reductant was boldine. As most of the alkaloids chelated and reduced the ferric ions, additional experimental studies are needed to elucidate the biological relevance of these results, as chelation is expected to block reactive oxygen species formation, while reduction could have the opposite effect.

• Klíčová slova
• alkaloid, chelation, copper, iron, reduction,
• MeSH
• Alzheimerova nemoc * MeSH
• chelátory chemie   MeSH
• cytostatické látky * MeSH
• dimethylsulfoxid MeSH
• galantamin MeSH
• hydroxylový radikál MeSH
• isochinoliny farmakologie   MeSH
• lidé MeSH
• měď chemie   MeSH
• reaktivní formy kyslíku MeSH
• redukční činidla MeSH
• soli MeSH
• železo chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chelátory MeSH
• cytostatické látky * MeSH
• dimethylsulfoxid MeSH
• galantamin MeSH
• hydroxylový radikál MeSH
• isochinoliny MeSH
• měď MeSH
• reaktivní formy kyslíku MeSH
• redukční činidla MeSH
• soli MeSH
• železo MeSH