β-Phenylethylamines and the isoquinoline alkaloids

Bentley, K. W.

doi:10.1039/np9890600405

Cited by 14 publications

(7 citation statements)

References 29 publications

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“…Secoberberines such as 5 ′ and 7 are structurally unique and are currently commercially inaccessible. Thus, few studies have been conducted on secoberberine-based drug development 39 40 41 42 43 44 45 46 . In addition, the structure of 7 synthesized by CYP82X1 has not been confirmed due to the lack of authentic standards and limited quantity of the compound achieved in the in vitro investigations 47 .…”

Section: Resultsmentioning

confidence: 99%

“…Noscapine is a phthalideisoquinoline alkaloid synthesized from L -tyrosine through scoulerine 36 , and the biosynthesis scheme involves multiple types of alkaloids, including 1-benzylisoquinoline, protoberberine and secoberberine alkaloids 37 38 . Among them, secoberberine alkaloids exhibit a unique structural scaffold, but their pharmacological activities are less investigated than alkaloids such as 1-benzylisoquinoline, protoberberine or phthalideisoquinoline alkaloids 39 40 41 42 43 44 45 46 , which may be due to limited access to these molecules.…”

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confidence: 99%

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Engineering biosynthesis of the anticancer alkaloid noscapine in yeast

2016

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Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides structural validation of the secoberberine intermediates and the description of the narcotoline-4′-O-methyltransferase, suggesting this activity is catalysed by a unique heterodimer. We also reconstitute a 14-step biosynthetic pathway of noscapine from the simple alkaloid norlaudanosoline by engineering a yeast strain expressing 16 heterologous plant enzymes, achieving reconstitution of a complex plant pathway in a microbial host. Other engineered yeasts produce previously inaccessible pathway intermediates and a novel derivative, thereby advancing protoberberine and noscapine related drug discovery.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Engineering biosynthesis of the anticancer alkaloid noscapine in yeast

2016

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“…As a result, the Menispermaceae family have been in a focus of rising interest to study several classes of secondary plant metabolites, including alkaloids; which are rather abundant constituents [4][5][6][7][8][9][10][11]. Several classes of alkaloids were isolated from Abuta, those include: isoquinoline [12,13], benzylisoquinoline [12,14], benzyltetraisoquinoline [15], bisbenzyltetraisoquinoline [15][16][17], aporphine [18], and proaporphine [12,15] derivatives; as well as other less frequent ones such as tropolone-isoquinoline, azafluoranthene, and benzazepine alkaloids [19,20]. Those alkaloids reveal a wide range of pharmacological activities including muscle relaxant [1], antiplasmodial [14], inhibitory for acetylcholinesterase (AChE) and butyrylacetylcholinesterase enzymes [17,21,22], cytotoxic [19,23,24], and immunomodulatory [25].…”

Section: Introductionmentioning

confidence: 99%

Alkaloids of Abuta panurensis Eichler: In silico and in vitro study of acetylcholinesterase inhibition, cytotoxic and immunomodulatory activities

et al. 2020

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Natural products obtained from species of the genus Abuta (Menispermaceae) are known as ethnobotanicals that are attracting increasing attention due to a wide range of their pharmacological properties. In this study, the alkaloids stepharine and 5-N-methylmaytenine were first isolated from branches of Abuta panurensis Eichler, an endemic species from the Amazonian rainforest. Structure of the compounds was elucidated by a combination of 1D and 2D NMR spectroscopic and MS and HRMS spectrometric techniques. Interaction of the above-mentioned alkaloids with acetylcholinesterase enzyme and interleukins IL-6 and IL-8 was investigated in silico by molecular docking. The molecules under investigation were able to bind effectively with the active sites of the AChE enzyme, IL-6, and IL-8 showing affinity towards the proteins. Along with the theoretical study, acetylcholinesterase enzyme inhibition, cytotoxic, and immunomodulatory activity of the compounds were assessed by in vitro assays. The data obtained in silico corroborate the results of AChE enzyme inhibition, the IC 50 values of 61.24μM for stepharine and 19.55μM for 5-N-methylmaytenine were found. The compounds showed cytotoxic activity against two tumor cell lines (K562 and U937) with IC 50 values ranging from 11.77 μM to 28.48 μM. The in vitro assays revealed that both alkaloids were non-toxic to Vero and human PBMC cells. As for the immunomodulatory activity, both compounds inhibited the production of IL-6 at similar levels. Stepharine inhibited considerably the production of IL-8 in comparison to 5-N-methylmaytenine, which showed a dose dependent action (inhibitory at the IC 50 dose, and stimulatory at the twofold IC 50 one). Such a behavior may possibly be explained by different binding modes of the alkaloids to the interleukin structural fragments. Occurrence of the polyamine alkaloid

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“…5 Cotarnine (2), a natural THIQ alkaloid, is isolated from Papaver pseudo-orientale. 12 It is one of noscapine's oxidative degradation products. Cotarnine hydrochloride is employed as a hemostatic agent and is the key component in the synthesis of tritoqualine, which is an antiallergic drug.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Functional Studies on Noscapine and Cotarnine Amino Acid Derivatives as Antitumor Agents

Davarzani,

Salehi,

Asghari

et al. 2023

ACS Omega

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β-Phenylethylamines and the isoquinoline alkaloids

Cited by 14 publications

References 29 publications

Engineering biosynthesis of the anticancer alkaloid noscapine in yeast

Engineering biosynthesis of the anticancer alkaloid noscapine in yeast

Alkaloids of Abuta panurensis Eichler: In silico and in vitro study of acetylcholinesterase inhibition, cytotoxic and immunomodulatory activities

Design, Synthesis, and Functional Studies on Noscapine and Cotarnine Amino Acid Derivatives as Antitumor Agents

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