β-Phenylethylamines and the isoquinoline alkaloids

Bentley, K. W.

doi:10.1039/b009713f

Cited by 23 publications

(6 citation statements)

References 163 publications

(194 reference statements)

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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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“…The isoquinoline ring system is present in numerous naturally occurring heterocyclic alkaloids that show a broad spectrum of biological activities. − For instance, natural isoquinoline alkaloids like berberine, palmatine, coralyne, and sanguinarine derivatives exhibit potent DNA binding properties. − It has been reported that isoquinoline alkaloids and some of its semisynthetic derivatives can interact with DNA G-quadruplexes. − Recently, natural isoquinoline alkaloids isolated from Chelidonium majus have been demonstrated as potent stabilizers of telomeric G-quadruplex DNA and inhibitors of telomerase enzyme . In the present study, 6-fluoroisoquinoline core was chosen as a suitable starting scaffold for generating G-quadruplex DNA-selective ligands, because of its chemical accessibility and polyaromatic planar surface that is favorable for stacking interactions with the external G-tetrads.…”

Section: Results and Discussionmentioning

confidence: 99%

Human Telomeric G-Quadruplex Selective Fluoro-Isoquinolines Induce Apoptosis in Cancer Cells

et al. 2018

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Small molecules that stabilize G-quadruplex structures in telomeres can prevent telomerase enzyme mediated telomere lengthening and subsequently lead to cell death. We herein report two fluoro-isoquinoline derivatives IQ1 and IQ2 as selective ligands for human telomeric G-quadruplex DNA. IQ1 and IQ2 containing different triazolyl side chains have been synthesized by Cu (I) catalyzed azide-alkyne cycloaddition. Fluorescence Resonance Energy Transfer (FRET) melting assay and fluorescence binding titrations indicate that both these ligands exhibit binding preference for telomeric G-quadruplex DNA ( h-TELO) over other promoter DNA quadruplexes and duplex DNA. However, ligand IQ1, containing pyrrolidine side chains, is capable of discriminating among quadruplexes by showing higher affinity toward h-TELO quadruplex DNA. On the contrary, IQ2, containing benzamide side chains, interacts with all the investigated quadruplexes. NMR analysis suggests that IQ1 interacts strongly with the external G-quartets of h-TELO. Biological studies reveal that IQ1 is more potent than IQ2 in inhibiting telomerase activity by selectively interacting with telomeric DNA G-quadruplex. Moreover, a dual luciferase reporter assay indicates that IQ1 is unable to reduce the cellular expression of c-MYC and BCL2 at transcriptional level. Significantly, IQ1 mostly stains the nucleus, induces cell cycle arrest in G0/G1 phase, triggers apoptotic response in cancer cells, and activates caspases 3/7.

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“…Aristolactams ( 113 – 116 ) along with aristolochic acids ( 117 , 118 ) and 4,5-dioxoaporphines ( 119 , 120 ) were mainly isolated from Aristolochiaceae but can also be found in several other plant species (Table 1) [87–92]. Several comprehensive overviews of various aristolactams were published by Shamma, Parmar and Bentley [87,92–95]. …”

Section: Reviewmentioning

confidence: 99%

The chemistry of isoindole natural products

Speck¹,

Magauer²

2013

Beilstein J. Org. Chem.

316

163

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SummaryThis review highlights the chemical and biological aspects of natural products containing an oxidized or reduced isoindole skeleton. This motif is found in its intact or modified form in indolocarbazoles, macrocyclic polyketides (cytochalasan alkaloids), the aporhoeadane alkaloids, meroterpenoids from Stachybotrys species and anthraquinone-type alkaloids. Concerning their biological activity, molecular structure and synthesis, we have limited this review to the most inspiring examples. Within different congeners, we have selected a few members and discussed the synthetic routes in more detail. The putative biosynthetic pathways of the presented isoindole alkaloids are described as well.

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β-Phenylethylamines and the isoquinoline alkaloids

Cited by 23 publications

References 163 publications

Engineering biosynthesis of the anticancer alkaloid noscapine in yeast

Engineering biosynthesis of the anticancer alkaloid noscapine in yeast

Human Telomeric G-Quadruplex Selective Fluoro-Isoquinolines Induce Apoptosis in Cancer Cells

The chemistry of isoindole natural products

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