Simple Isoquinoline Alkaloids

Menachery, Mary D.; Lavanier, Gregory L.; Wetherly, M. L.; Guinaudeau, Hélène; Shamma, Maurice

doi:10.1021/np50047a001

Cited by 73 publications

(21 citation statements)

References 105 publications

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“…The GC/MS investigation resulted in the identification of four main tetrahydroisoquinoline alkaloids by their MS fragmentation patterns as major components of the ethyl acetate extracts (Figure 1). Identification was made also by comparison of their spectral fragmentation with those reported in the literature [34]. In relation to the mass fragmentation pattern, the ions at m/z 192, 178 and 149 are characteristic.…”

Section: Alkaloids Contentmentioning

confidence: 99%

A potential role of alkaloid extracts from Salsola species (Chenopodiaceae) in the treatment of Alzheimer's disease

Tundis

Conforti

Loizzo

et al. 2009

Journal of Enzyme Inhibition and Medicinal Chemistry

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From the aerial parts of Salsola oppositofolia, S. soda and S. tragus an alkaloid extract was obtained and tested to evaluate antioxidant and anti-cholinesterase activities. The in vitro study of the antioxidant activity by the DPPH method revealed a significant activity of Salsola alkaloid extracts with IC 50 values ranging from 16.30 mg/mL for S. oppositifolia to 26.17 mg/mL for S. tragus. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were evaluated. S. tragus alkaloid extract exerted the highest inhibitory activity against AChE (IC 50 of 30.2 mg/mL) and BChE (IC 50 of 26.5 mg/mL). Interestingly, S. soda and S. oppositifolia exhibited a selective inhibitory activity against BChE with IC 50 values of 34.3 mg/mL and 32.7 mg/mL, respectively. Tetrahydroisoquinoline alkaloids were identified and quantified by GC/MS analysis.

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Section: Alkaloids Contentmentioning

confidence: 99%

A potential role of alkaloid extracts from Salsola species (Chenopodiaceae) in the treatment of Alzheimer's disease

Tundis

Conforti

Loizzo

et al. 2009

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…[10][11][12][13][14][15][16][17][18][19][20] Most of the available nAChR antagonists are natural products such as methyllycaconitine (MLA), αbungarotoxin, ibogaine, d-tubocurarine, α-conotoxins and dihydro-β-erythroidine (DHβE), the latter being a widely used selective antagonist of β2-containing heteromeric nAChRs and a semisynthetic member of the Erythrina alkaloid family. 21,22 We recently reported the design, synthesis and pharmacological evaluation of 21 analogs of aromatic Erythrina alkaloids as nAChR antagonists and found that the structurally simple tetrahydroisoquinoline 1 (also known as O-methylcorypalline) 23,24 displayed submicromolar binding affinity at the α4β2 nAChR and more than 300-fold binding selectivity over the α4β4, α3β4 and α7 subtypes (see Figure 1A). 25 Ligands containing quaternary nitrogens have previously been shown to possess high activity at the nAChR.…”

Section: Introductionmentioning

confidence: 99%

Dual Nicotinic Acetylcholine Receptor α4β2 Antagonists/α7 Agonists: Synthesis, Docking Studies, and Pharmacological Evaluation of Tetrahydroisoquinolines and Tetrahydroisoquinolinium Salts

et al. 2018

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We describe the synthesis of tetrahydroisoquinolines and tetrahydroisoquinolinium salts together with their pharmacological properties at various nicotinic acetylcholine receptors. In general, the compounds were α4β2 nAChR antagonists, with the tetrahydroisoquinolinium salts being more potent than the parent tetrahydroisoquinoline derivatives. The most potent α4β2 antagonist, 6c, exhibited submicromolar binding K and functional IC values and high selectivity for this receptor over the α4β4 and α3β4 nAChRs. Whereas the (S)-6c enantiomer was essentially inactive at α4β2, (R)-6c was a slightly more potent α4β2 antagonist than the reference β2-nAChR antagonist DHβΕ. The observation that the α4β2 activity resided exclusively in the (R)-enantiomer was in full agreement with docking studies. Several of tetrahydroisoquinolinium salts also displayed agonist activity at the α7 nAChR. Preliminary in vivo evaluation revealed antidepressant-like effects of both (R)-5c and (R)-6c in the mouse forced swim test, supporting the therapeutic potential of α4β2 nAChR antagonists for this indication.

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“…The isoquinoline ring system has considerable relevance in drug development, since it is found in both complex [1] and “simple” alkaloids (variously substituted derivatives of the native isoquinoline) isolated from different plants [2], and antiviral and antimicrobial activities have been found for numerous isoquinoline alkaloids [3]. Further, isoquinoline is regarded as a “privileged scaffold” in drug design, and a large number of drug candidates containing this partial structure are in clinical development [4].…”

Section: Introductionmentioning

confidence: 99%

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

Melzer

Felber

Bracher

2018

Beilstein J. Org. Chem.

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Highly-substituted isoquinolines are important scaffolds in syntheses of natural products and in drug development and hence, effective synthetic approaches are required. Here we present a novel method for the introduction of a methyl group at C1 of isoquinolines. This is exemplified by a new total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline. Direct metalation of 7-benzyloxy-6-methoxyisoquinoline with Knochel-Hauser base, followed by cuprate-mediated methylation gives the target alkaloid directly, but separation from the educt is cumbersome. Quenching the metalated intermediate with Eschenmoser's reagent gives an easy to clean tertiary benzylamine, which, after quaternization with iodomethane, is easily converted into the desired 1-methylisoquinoline by hydrogenolysis of both the benzylamine and benzyl ether groups. 130

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Simple Isoquinoline Alkaloids

Cited by 73 publications

References 105 publications

A potential role of alkaloid extracts from Salsola species (Chenopodiaceae) in the treatment of Alzheimer's disease

A potential role of alkaloid extracts from Salsola species (Chenopodiaceae) in the treatment of Alzheimer's disease

Dual Nicotinic Acetylcholine Receptor α4β2 Antagonists/α7 Agonists: Synthesis, Docking Studies, and Pharmacological Evaluation of Tetrahydroisoquinolines and Tetrahydroisoquinolinium Salts

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

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