Application of HPLC-DAD for In Vitro Investigation of Acetylcholinesterase Inhibition Activity of Selected Isoquinoline Alkaloids from Sanguinaria canadensis Extracts

Tuzimski, Tomasz; Petruczynik, Anna

doi:10.3390/molecules26010230

Cited by 8 publications

(9 citation statements)

References 36 publications

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“…Berberine, a natural isoquinoline alkaloid often isolated from the Chinese herb Rhizoma coptidis, displays a plethora of biologically active properties and similar to sanguinarine, can also induce cytotoxicity [68]. Berberine displays relatively potent anti-AChE binding and inhibitory activity, with IC 50 values of approximately 0.3-3 µM, in line with theoretical Kd values [29,37,51,66,67,[69][70][71]. In comparison, berberine is a weaker inhibitor of BuChE with IC 50 values in the range of 3-18 µM (for equine BuChE) [69,70].…”

Section: Discussionsupporting

confidence: 57%

“…Sanguinarine has purported anticancer activities [64] but may also be carcinogenic itself [65]. Sanguinarine has relatively potent anti-AChE activity with IC 50 values calculated at approximately 5.6 µM by a highperformance liquid chromatography (HPLC) assay [66] and as low as 0.8 µM via a kinetic assay (of human AChE) [67]; values in keeping with a theoretically high affinity for human AChE (Table 1). By comparison, inhibition of BuChE is weaker, with sanguinarine 14 times less potent an inhibitor of human BuChE than human AChE [67].…”

Section: Discussionmentioning

confidence: 92%

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In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer’s Disease

Amat-ur-Rasool

Ahmed

Hasnain

et al. 2021

CIMB

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The number of patients with neurodegenerative diseases, particularly Alzheimer’s disease (AD), continues to grow yearly. Cholinesterase inhibitors (ChEIs) represent the first-line symptomatic drug treatment for mild-to-moderate AD; however, there is an unmet need to produce ChEIs with improved efficacy and reduced side effects. Herein, phytochemicals with reported anti-acetylcholinesterase (AChE) activity were ranked in silico for their anti-AChE potential. Ligands with a similar or higher binding affinity to AChE than galantamine were then selected for the design of novel dual-binding site heterodimeric drugs. In silico molecular docking of heterodimers with the target enzymes, AChE and butyrylcholinesterase (BuChE), were performed, and anti-cholinesterase binding affinities were compared with donepezil. Drug-likeliness properties and toxicity of the heterodimers were assessed using the SwissADME and ProTox-II webservers. Nine phytochemicals displayed similar or higher binding affinities to AChE than galantamine: sanguinarine > huperzine A > chelerythrine > yohimbine > berberine > berberastine > naringenin > akuammicine > carvone. Eleven heterodimeric ligands were designed with phytochemicals separated by four- or five-carbon alkyl-linkers. All heterodimers were theoretically potent AChE and BuChE dual-binding site inhibitors, with the highest affinity achieved with huperzine-4C-naringenin, which displayed 34% and 26% improved affinity to AChE and BuChE, respectively, then the potent ChEI drug, donepezil. Computational pharmacokinetic and pharmacodynamic screening suggested that phytochemical heterodimers would display useful gastrointestinal absorption and with relatively low predicted toxicity. Collectively, the present study suggests that phytochemicals could be garnered for the provision of novel ChEIs with enhanced drug efficacy and low toxicity.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 92%

In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer’s Disease

Amat-ur-Rasool

Ahmed

Hasnain

et al. 2021

CIMB

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“…Typically, chromatograms obtained for plant extracts are presented in Figures S1 and S2. Chromatogram obtained for extracts from Sanguinaria canadensis collected during flowering was presented earlier [24]. The highest contents of sanguinarine and chelerythrine were found in The quantitative determination of selected isoquinoline alkaloids in plant extracts were performed in the same chromatographic conditions.…”

Section: Alkaloidmentioning

confidence: 99%

“…Alkaloid standards (see Table 1) were chromatographed in condition, based on the previously published method applied for determination of isoquinoline alkaloids, after appropriate modification [24]. Separation was performed on the Polar Reversed Phase (RP) column with the eluent system containing acetonitrile, water, and 0.04 ML −1 of 1-butyl-3-methylimidazolium tetrafluoroborate, in a gradient system described in the section "Experimental".…”

Section: Hplc-dad and Lc-ms/ms Analysis Of Alkaloid Standards And Plant Extractsmentioning

confidence: 99%

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Determination of Cytotoxic Activity of Sanguinaria canadensis Extracts against Human Melanoma Cells and Comparison of Their Cytotoxicity with Cytotoxicity of Some Anticancer Drugs

et al. 2021

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Melanoma is an enormous global health burden, and should be effectively addressed with better therapeutic strategies. Therefore, new therapeutic agents are needed for the management of this disease. The aim of this study was the investigation of cytotoxic activity of some isoquinoline alkaloid standards and extracts obtained from Sanguinaria canadensis—collected before, during, and after flowering—against three different human melanoma cells (A375, G361, SK-MEL-3). The cytotoxicity of these extracts was not previously tested on these melanoma cell lines. Determination of alkaloid contents was performed by HPLC-DAD using Polar RP column and mobile phase containing acetonitrile, water, and 1-butyl-3-methylimidazolium tetrafluoroborate. The cytotoxicity of alkaloid standards was investigated by determination of cell viability and calculation of IC50 values. Significant differences were observed in the alkaloids content and cytotoxic activity of the extracts, depending on the season of collection of the plant material. In the Sanguinaria canadensis extracts high contents of sanguinarine (from 4.8543 to 9.5899 mg/g of dry plant material) and chelerythrine (from 42.7224 to 6.8722 mg/g of dry plant material) were found. For both of these alkaloids, very high cytotoxic activity against the tested cell lines were observed. The IC50 values were in the range of 0.11–0.54 µg/mL for sanguinarine and 0.14 to 0.46 µg/mL for chelerythrine. IC50 values obtained for Sanguinaria canadensis extracts against all tested cell lines were also very low (from 0.88 to 10.96 µg/mL). Cytotoxic activity of alkaloid standards and Sanguinaria canadensis extracts were compared with the cytotoxicity of anticancer drugs—etoposide, cisplatin, and hydroxyurea. In all cases except the one obtained for cisplatin against A375, which was similar to that obtained for Sanguinaria canadensis after flowering against the same cell line, IC50 values obtained for anticancer drugs were higher than the IC50 values obtained for sanguinarine, chelerythrine, and Sanguinaria canadensis extracts. Our results showed that Sanguinaria canadensis extracts and isoquinoline alkaloids, especially sanguinarine and chelerythrine, could be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of human melanomas.

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Cholinesterase Inhibitory and In Silico Toxicity Assessment of Thirty-Four Isoquinoline Alkaloids - Berberine as the Lead Compound

Orhan

Deniz

Salmas

et al. 2024

CNSNDDT

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Background:: Cholinesterase (ChE) inhibitors used currently in clinics for the treatment of Alzheimer’s disease (AD) are the most prescribed drug class with nitrogen-containing chemical formula. Galanthamine, the latest generation anti-ChE drug, contains an isoquinoline structure Objective:: The aim of the current study was to investigate the inhibitory potential of thirty-four isoquinoline alkaloids, e.g. (-)-adlumidine, β-allocryptopine, berberine, (+)-bicuculline, (-)-bicuculline, (+)-bulbocapnine, (-)-canadine, (±)-chelidimerine, corydaldine, (±)-corydalidzine, (-)-corydalmine, (+)-cularicine, dehydrocavidine, (+)-fumariline, (-)-fumarophycine, (+)-α-hydrastine, (+)-isoboldine, 13-methylcolumbamine, (-)-norjuziphine, norsanguinarine, (-)-ophiocarpine, (-)-ophiocarpine-N-oxide, oxocularine, oxosarcocapnine, palmatine, (+)-parfumine, protopine, (+)-reticuline, sanguinarine, (+)-scoulerine, (±)-sibiricine, (±)-sibiricine acetate, (-)-sinactine, and (-)-stylopine isolated from several Fumaria (fumitory) and Corydalis species towards acetyl- (AChE) and butyrylcholinesterase (BChE) by microtiter plate assays. The alkaloids with strong ChE inhibition were proceeded to molecular docking simulations as well as in silico toxicity screening for their mutagenic capacity through VEGA QSAR (AMES test) consensus model and VEGA platform as statistical approaches. The inputs were evaluated in a simplified molecular input-line entry system (SMILES). Results:: ChE inhibition assays indicated that the highest AChE inhibition was caused by berberine (IC50: 0.72 ± 0.04 µg/mL), palmatine (IC50: 6.29 ± 0.61 µg/mL), β-allocryptopine (IC50: 10.62 ± 0.45 µg/mL), (-)-sinactine (IC50: 11.94 ± 0.44 µg/mL), and dehydrocavidine (IC50: 15.01 ± 1.87 µg/mL) as compared to that of galanthamine (IC50: 0.74 ± 0.01 µg/mL), the reference drug with isoquinoline skeleton. Less number of the tested alkaloids exhibited notable BChE inhibition. Among them, berberine (IC50: 7.67 ± 0.36 µg/mL) and (-)-corydalmine (IC50: 7.78 ± 0.38 µg/mL) displayed a stronger inhibition than that of galanthamine (IC50: 12.02 ± 0.25 µg/mL). The mutagenic activity was shown for β-allocryptopine, (+)- and (-)-bicuculline, (±)-corydalidzine, (-)-corydalmine, (+)-cularicine, (-)-fumarophycine, (-)-norjuziphine, (-)-ophiocarpine-N-oxide, (+)-scoulerine, (-)-sinactine, and (-)-stylopine by means of in silico experiments. The results obtained by molecular docking simulations of berberine, palmatine, and (-)-corydalmine suggested that the estimated free ligand-binding energies of these compounds inside the binding domains of their targets are reasonable to make them capable of establishing strong polar and nonpolar bonds with the atoms of the active site amino acids. method: The alkaloids with strong inhibition were proceeded to molecular docking simulations as well as in silico toxicity screening for their mutagenic capacity through VEGA QSAR (AMES test) consensus model and VEGA platform as statistical approaches. The inputs were evaluated in a simplified molecular input-line entry system &#40;SMILES&#41;. Conclusion:: Our findings revealed that berberine, palmatin, and (-)-corydalmine stand out as the most promising isoquinoline alkaloids in terms of ChE inhibition. Among them, berberine has displayed a robust dual inhibition against both ChEs and could be evaluated further as a lead compound for AD. other: -

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Application of HPLC-DAD for In Vitro Investigation of Acetylcholinesterase Inhibition Activity of Selected Isoquinoline Alkaloids from Sanguinaria canadensis Extracts

Cited by 8 publications

References 36 publications

In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer’s Disease

In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer’s Disease

Determination of Cytotoxic Activity of Sanguinaria canadensis Extracts against Human Melanoma Cells and Comparison of Their Cytotoxicity with Cytotoxicity of Some Anticancer Drugs

Cholinesterase Inhibitory and In Silico Toxicity Assessment of Thirty-Four Isoquinoline Alkaloids - Berberine as the Lead Compound

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