Benzylisoquinoline Alkaloids from the Papaveraceae: The Heritage of Johannes Gadamer (1867–1928)

Meyer, A. B.; Imming, Peter

doi:10.1021/np2005049

Cited by 16 publications

(6 citation statements)

References 34 publications

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“…Another indication is the major reduction over time in the use of crystallization as a classic method for purification. 10 Crystallization also requires sufficient quantities of material, and even though small samples of materials may be crystallized, the use of this purification procedure may be precluded because of limitations in the handling of small sample volumes and the unavoidable material losses encountered during the process. While X-ray crystallographers employ low temperature techniques for obtaining small quantities of crystalline material, these methods are not practiced in a routine manner for small molecule purification.…”

Section: Introductionmentioning

confidence: 99%

Importance of Purity Evaluation and the Potential of Quantitative ¹H NMR as a Purity Assay

Pauli¹,

Chen²,

Simmler³

et al. 2014

J. Med. Chem.

327

290

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In any biomedical and chemical context, a truthful description of chemical constitution requires coverage of both structure and purity. This qualification affects all drug molecules, regardless of development stage (early discovery to approved drug) and source (natural product or synthetic). Purity assessment is particularly critical in discovery programs and whenever chemistry is linked with biological and/or therapeutic outcome. Compared with chromatography and elemental analysis, quantitative NMR (qNMR) uses nearly universal detection and provides a versatile and orthogonal means of purity evaluation. Absolute qNMR with flexible calibration captures analytes that frequently escape detection (water, sorbents). Widely accepted structural NMR workflows require minimal or no adjustments to become practical 1H qNMR (qHNMR) procedures with simultaneous qualitative and (absolute) quantitative capability. This study reviews underlying concepts, provides a framework for standard qHNMR purity assays, and shows how adequate accuracy and precision are achieved for the intended use of the material.

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Section: Introductionmentioning

confidence: 99%

Importance of Purity Evaluation and the Potential of Quantitative ¹H NMR as a Purity Assay

Pauli¹,

Chen²,

Simmler³

et al. 2014

J. Med. Chem.

327

290

View full text Add to dashboard Cite

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“…The isoquinoline alkaloids 1-8, 10-17, and 20-39 have been described in our previous studies (Meyer and Imming, 2011;Salminen et al, 2011b); alkaloids 40 and 42 are synthetic, and 9 and 41 are semisynthetic derivatives of 23 (tetrahydropalmatine) (unpublished data). Alkaloids 18-19 and 43-49 were purchased from Sigma-Aldrich (St. Louis, MO) and were of the highest purity available.…”

Section: Chemicalsmentioning

confidence: 82%

Time-Dependent Inhibition of CYP2C19 by Isoquinoline Alkaloids: In Vitro and In Silico Analysis

Salminen

Rahnasto-Rilla

Väänänen

et al. 2015

Drug Metabolism and Disposition

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The cytochrome P450 2C19 (CYP2C19) enzyme plays an important role in the metabolism of many commonly used drugs. Relatively little is known about CYP2C19 inhibitors, including compounds of natural origin, which could inhibit CYP2C19, potentially causing clinically relevant metabolism-based drug interactions. We evaluated a series (N = 49) of structurally related plant isoquinoline alkaloids for their abilities to interact with CYP2C19 enzyme using in vitro and in silico methods. We examined several common active alkaloids found in herbal products such as apomorphine, berberine, noscapine, and papaverine, as well as the previously identified mechanism-based inactivators bulbocapnine, canadine, and protopine. The IC 50 values of the alkaloids ranged from 0.11 to 210 mM, and 42 of the alkaloids were confirmed to be time-dependent inhibitors of CYP2C19. Molecular docking and three-dimensional quantitative structure-activity relationship analysis revealed key interactions of the potent inhibitors with the enzyme active site. We constructed a comparative molecular field analysis model that was able to predict the inhibitory potency of a series of independent test molecules. This study revealed that many of these isoquinoline alkaloids do have the potential to cause clinically relevant drug interactions. These results highlight the need for studying more profoundly the potential interactions between drugs and herbal products. When further refined, in silico methods can be useful in the high-throughput prediction of P450 inhibitory potential of pharmaceutical compounds.

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“…Biomedical Research and Therapy 2018, 5(6) a perennial medicinal plant from the Papaveraceae family. Its major chemical constituents are benzylisoquinoline alkaloids, flavonoids and organic acids like fumaric acid [13] .…”

Section: Eghbalian Et Almentioning

confidence: 99%

Comparison of the efficacy and tolerability of an oral dosage form made from Fumaria vaillantii versus cetirizinein management of chronic urticaria: A single-blind, randomized, clinical trial

et al. 2018

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BACKGROUND: Chronic urticaria (CU) is one of the common allergic diseases whose conventional treatments have failed to desirably manage it. Fumariavaillantii is used in Persian medicine to treat CU. The anti-inflammatory and anti-histaminic effects of chemical components of Fumaria such as fumaric acid and caffeic acid were confirmed. Dimethyl fumarate reduces the pro- inflammatory contribution and monomethyl fumarate can increase IL-4, an antiinflammatory interleukin, or can decrease IFN- , an inflammatory factor. The current study assesses the efficacy and tolerability of Fumaria vaillantii versus cetirizine in the management of CU. METHODS: The formulation and standardization of Fumaria syrup were done in Tehran University of Medical Sciences. Patients were randomized to twice- daily treatment with Fumaria syrup or cetirizine syrup (n=39 in each group) for four weeks. The efficacy assessment included Urticaria Activity Score (UAS) and Chronic Urticaria Quality of Life Questionnaire (CUQ2oL) and the safety evaluations included Common Terminology Criteria for Adverse Events Questionnaire. RESULTS: The fumaric acid content in 5 ml of Fumaria syrup was calculated to be 0.12 mg. The results of clinical trial showed that UAS was significantly higher in the Fumaria group than in the cetirizine group, after the first week of follow-up (p<0.001), but no significant difference was demonstrated between the two groups on week 4 (p=0.57). One month after the research was finished, the UAS score of the cetirizine group was significantly higher than that of the Fumaria group (p<0.001). After finishing the interventions, difference of CU-Q2oL was not significant between the two groups; however, the QOL score was significantly lower in the Fumaria group (p<0.001) at 8th week. About adverse events, the incidence of somnolence in the Fumaria group was significantly lower than in the cetirizine group (p<0.001). CONCLUSIONS: Fumaria vaillantii demonstrated its effects on CU later than cetirizine, but led to more permanent effects, better quality of life, and lower incidence of adverse events as compared to cetirizine. More clinical trials with higher populations are needed to achieve more conclusive results.

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Benzylisoquinoline Alkaloids from the Papaveraceae: The Heritage of Johannes Gadamer (1867–1928)

Cited by 16 publications

References 34 publications

Importance of Purity Evaluation and the Potential of Quantitative ¹H NMR as a Purity Assay

Importance of Purity Evaluation and the Potential of Quantitative ¹H NMR as a Purity Assay

Time-Dependent Inhibition of CYP2C19 by Isoquinoline Alkaloids: In Vitro and In Silico Analysis

Comparison of the efficacy and tolerability of an oral dosage form made from Fumaria vaillantii versus cetirizinein management of chronic urticaria: A single-blind, randomized, clinical trial

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Benzylisoquinoline Alkaloids from the Papaveraceae: The Heritage of Johannes Gadamer (1867–1928)

Cited by 16 publications

References 34 publications

Importance of Purity Evaluation and the Potential of Quantitative 1H NMR as a Purity Assay

Importance of Purity Evaluation and the Potential of Quantitative 1H NMR as a Purity Assay

Time-Dependent Inhibition of CYP2C19 by Isoquinoline Alkaloids: In Vitro and In Silico Analysis

Comparison of the efficacy and tolerability of an oral dosage form made from Fumaria vaillantii versus cetirizinein management of chronic urticaria: A single-blind, randomized, clinical trial

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Importance of Purity Evaluation and the Potential of Quantitative ¹H NMR as a Purity Assay

Importance of Purity Evaluation and the Potential of Quantitative ¹H NMR as a Purity Assay