Canadine

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Canadine
Canadine structure.svg
Names
IUPAC name
9,10-Dimethoxy-2′H-[1,3]dioxolo[4′,5′:2,3]berbine
Systematic IUPAC name
(13aS)-9,10-Dimethoxy-5,8,13,13a-tetrahydro-2H,6H-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinoline
Other names
(S)-Tetrahydroberberine; Xanthopuccine
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.023.468 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C20H21NO4/c1-22-17-4-3-12-7-16-14-9-19-18(24-11-25-19)8-13(14)5-6-21(16)10-15(12)20(17)23-2/h3-4,8-9,16H,5-7,10-11H2,1-2H3/t16-/m0/s1
    Key: VZTUIEROBZXUFA-INIZCTEOSA-N
  • O1c2c(OC1)cc3c(c2)CCN5[C@H]3Cc4ccc(OC)c(OC)c4C5
Properties
C20H21NO4
Molar mass 339.391 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

(S)-Canadine, also known as (S)-tetrahydroberberine and xanthopuccine, is a benzylisoquinoline alkaloid (BIA), of the protoberberine structural subgroup, and is present in many plants from the family Papaveraceae, such as Corydalis yanhusuo and C. turtschaninovii .

Contents

Biosynthesis

Metabolically, (S)-canadine is derived from (S)-reticuline, a pivotal intermediate in the biosynthesis of numerous BIA structural subgroups, through three enzymatic steps: 1) Berberine bridge enzyme to (S)-scoulerine; 2) (S)-scoulerine 9-O-methyltransferase to (S)-tetrahydrocolumbamine; and 3) (S)-canadine synthase/CYP719A21 to (S)-canadine. [1]

(S)-Canadine is the immediate metabolic precursor of berberine, which is obtained through the action of the enzyme (S)-tetrahydroprotoberberine oxidase. [1] It is also an intermediate in the complex biosynthesis of noscapine, which is likewise a benzylisoquinoline alkaloid, but of the phthalideisoquinoline structural subgroup. [2] [3]

(S)-Canadine, berberine, palmatine, and hydrastine are the major alkaloids present in goldenseal.

Effects

A number of in vitro effects of (S)-canadine have been reported. It stimulates myogenesis and inhibits muscle protein degradation. [4] (S)-Canadine blocks K(ATP) channels in dopamine neurons. [5] [6] (S)-Canadine has displayed antioxidant activity: though it lacked any demonstrable cytotoxic effect in three unique cell cultures, it was observed to possess antioxidant activity against free radical-induced oxidative injury. [7] [8] (S)-Canadine can block voltage-dependent calcium channels, but at a level significantly lower than that of verapamil. [9]

Related Research Articles

<span class="mw-page-title-main">Noscapine</span> Chemical compound

Noscapine is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the family Papaveraceae. It lacks significant hypnotic, euphoric, or analgesic effects affording it with very low addictive potential. This agent is primarily used for its antitussive (cough-suppressing) effects.

Neuraminidase inhibitors (NAIs) are a class of drugs which block the neuraminidase enzyme. They are a commonly used antiviral drug type against influenza. Viral neuraminidases are essential for influenza reproduction, facilitating viral budding from the host cell. Oseltamivir (Tamiflu), zanamivir (Relenza), laninamivir (Inavir), and peramivir belong to this class. Unlike the M2 inhibitors, which work only against the influenza A virus, NAIs act against both influenza A and influenza B.

<span class="mw-page-title-main">Scoulerine</span> Chemical compound

Scoulerine, also known as discretamine and aequaline, is a benzylisoquinoline alkaloid (BIA) that is derived directly from (S)-reticuline through the action of berberine bridge enzyme. It is a precursor of other BIAs, notably berberine, noscapine, (S)-tetrahydropalmatine, and (S)-stylopine, as well as the alkaloids protopine, and sanguinarine. It is found in many plants, including opium poppy, Croton flavens, and certain plants in the genus Erythrina.

<span class="mw-page-title-main">Berberine</span> Quaternary ammonium cation

Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids

In enzymology, a (S)-scoulerine 9-O-methyltransferase is an enzyme that catalyzes the chemical reaction

(S)-Tetrahydroberberine oxidase is an enzyme that catalyzes the final transformation in the biosynthesis of berberine, a quaternary benzylisoquinoline alkaloid of the protoberberine structural subgroup. This reaction pathway catalyzes the four-electron oxidation of (S)-tetrahydroberberine in the presence of oxygen to produce berberine and hydrogen peroxide as products.

In enzymology, a reticuline oxidase (EC 1.21.3.3) is an enzyme that catalyzes the chemical reaction

In enzymology, a (S)-canadine synthase (EC 1.14.21.5) is an enzyme that catalyzes the chemical reaction

The enzyme (S)-norcoclaurine synthase (EC 4.2.1.78) catalyzes the chemical reaction

<span class="mw-page-title-main">Higenamine</span> Chemical compound

Higenamine (norcoclaurine) is a chemical compound found in a variety of plants including Nandina domestica (fruit), Aconitum carmichaelii (root), Asarum heterotropioides, Galium divaricatum, Annona squamosa, and Nelumbo nucifera.

<span class="mw-page-title-main">Benzylisoquinoline</span> Chemical compound

Substitution of the heterocycle isoquinoline at the C1 position by a benzyl group provides 1‑benzylisoquinoline, the most widely examined of the numerous benzylisoquinoline structural isomers. The 1-benzylisoquinoline moiety can be identified within numerous compounds of pharmaceutical interest, such as moxaverine; but most notably it is found within the structures of a wide variety of plant natural products, collectively referred to as benzylisoquinoline alkaloids. This class is exemplified in part by the following compounds: papaverine, noscapine, codeine, morphine, apomorphine, berberine, tubocurarine.

<span class="mw-page-title-main">Protopine</span> Chemical compound

Protopine is an alkaloid occurring in opium poppy, Corydalis tubers and other plants of the family papaveraceae, like Fumaria officinalis. Protopine is metabolically derived from the benzylisoquinoline alkaloid (S)-Reticuline through a progressive series of five enzymatic transformations: 1) berberine bridge enzyme to (S)-Scoulerine; 2) (S)-cheilanthifoline synthase/CYP719A25 to (S)-Cheilanthifoline; 3) (S)-stylopine synthase/CYP719A20 to (S)-Stylopine; 4) (S)-tetrahydroprotoberberine N-methyltransferase to (S)-cis-N-Methylstylopine; and ultimately, 5) N-methylstylopine hydroxylase to protopine.

<span class="mw-page-title-main">Huang Bai</span> Herb in Chinese medicine

Huáng bǎi, huáng bó or huáng bò is one of the fifty fundamental herbs of traditional Chinese medicine. Known also as Cortex Phellodendri, it is the bark of one of two species of Phellodendron tree: Phellodendron amurense or Phellodendron chinense.

<span class="mw-page-title-main">Palmatine</span> Chemical compound

Palmatine is a protoberberine alkaloid found in several plants including Phellodendron amurense, Coptis Chinensis and Corydalis yanhusuo, Tinospora cordifolia, Tinospora sagittata, Phellodendron amurense, Stephania yunnanensis.

<span class="mw-page-title-main">Miquelianin</span> Chemical compound

Miquelianin is a flavonol glucuronide, a type of phenolic compound present in wine, in species of St John's wort, like Hypericum hirsutum, in Nelumbo nucifera or in green beans.

<span class="mw-page-title-main">Cheilanthifoline</span> Chemical compound

(S)-Cheilanthifoline is a benzylisoquinoline alkaloid (BIA) which has been isolated from Corydalis dubia and Argemone mexicana. (S)-Cheilanthifoline is metabolically derived from (S)-reticuline, a pivotal intermediate in the biosynthesis of numerous BIAs. (S)-Cheilanthifoline is the immediate precursor of the BIA (S)-stylopine ((S)-stylopine synthase/CYP719A20), which is the precursor for the alkaloids protopine and sanguinarine.

<span class="mw-page-title-main">Magnoflorine</span> Chemical compound

(S)-Magnoflorine is a quaternary benzylisoquinoline alkaloid (BIA) of the aporphine structural subgroup which has been isolated from various species of the family Menispermaceae, such as Pachygone ovata,Sinomenium acutum, and Cissampelos pareira. 

<span class="mw-page-title-main">BBE-like enzymes</span>

Berberine bridge enzyme-like form a subgroup of the superfamily of FAD-linked oxidases, structurally characterized by a typical fold observed initially for vanillyl-alcohol oxidase (VAO). This proteins are part of a multigene family (PF08031) that can be found in plants, fungi and bacteria.

<span class="mw-page-title-main">4-Hydroxyphenylacetaldehyde</span> Chemical compound

4-Hydroxyphenylacetaldehyde, also known as p-hydroxyphenylacetaldehyde, is a natural product with the formula HOC6H4CH2CHO. It is a derivative of phenylacetaldehyde and occurs as a white solid at room temperature.

<span class="mw-page-title-main">Aporphine alkaloids</span>

Aporphine alkaloids are naturally occurring chemical compounds from the group of alkaloids. After the benzylisoquinoline alkaloids they are the second largest group of isoquinoline alkaloids.

References

  1. 1 2 Hagel, Jillian M.; Morris, Jeremy S.; Lee, Eun-Jeong; Desgagne-Penix, Isabel; Bross, Crystal D.; Chang, Limei; Chen, Xue; Farrow, Scott C.; Zhang, Ye (2015). "Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants". BMC Plant Biology. 15: 227. doi:10.1186/s12870-015-0596-0. PMC   4575454 . PMID   26384972.
  2. Dang, Thu-Thuy T.; Facchini, Peter J. (2014). "CYP82Y1 is N-Methylcanadine 1-Hydroxylase, a Key Noscapine Biosynthetic Enzyme in Opium Poppy" (PDF). The Journal of Biological Chemistry. 289 (4): 2013–2026. doi: 10.1074/jbc.M113.505099 . PMC   3900951 . PMID   24324259.
  3. Chen, Xue; Facchini, Peter J. (2014). "Short-chain dehydrogenase/reductase catalyzing the final step of noscapine biosynthesis is localized to laticifers in opium poppy". The Plant Journal. 77 (2): 173–184. doi: 10.1111/tpj.12379 . PMID   24708518.
  4. Lee, Hyejin; Lee, Sang-Jin; Bae, Gyu-Un; Baek, Nam-In; Ryu, Jae-Ha (2017). "Canadine from Corydalis turtschaninovii Stimulates Myoblast Differentiation and Protects against Myotube Atrophy". International Journal of Molecular Sciences. 18 (12): 2748. doi: 10.3390/ijms18122748 . PMC   5751347 . PMID   29258243.
  5. Wu, Chen; Yang, Kechun; Liu, Qiang; Wakui, Matoko; Jin, Guo-zhang; Zhen, Xuechu; Wu, Jie (2010). "Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta". Neuropharmacology. 59 (7–8): 567–72. doi:10.1016/j.neuropharm.2010.08.018. PMID   20804776. S2CID   27386799.
  6. Wu, Jie; Jin, Guo Zhang (1997). "Tetrahydroberberine blocks membrane K+ channels underlying its inhibition of intracellular message-mediated outward currents in acutely dissociated CA1 neurons from rat hippocampus". Brain Research. 775 (1–2): 214–8. doi:10.1016/s0006-8993(97)00960-8. PMID   9439847. S2CID   42250453.
  7. Correché, Estela R.; Andujar, Sebastian A.; Kurdelas, Rita R.; Lechón, María J. Gómez; Freile, Mónica L.; Enriz, Ricardo D. (2008). "Antioxidant and cytotoxic activities of canadine: Biological effects and structural aspects". Bioorganic & Medicinal Chemistry. 16 (7): 3641–51. doi:10.1016/j.bmc.2008.02.015. PMID   18295494.
  8. Mari, Giacomo; Catalani, Simona; Antonini, Elena; De Crescentini, Lucia; Mantellini, Fabio; Santeusanio, Stefania; Lombardi, Paolo; Amicucci, Antonella; Battistelli, Serafina (2018). "Synthesis and biological evaluation of novel heteroring-annulated pyrrolino-tetrahydroberberine analogues as antioxidant agents". Bioorganic & Medicinal Chemistry. 26 (18): 5037–44. doi:10.1016/j.bmc.2018.08.038. PMID   30196978.
  9. Yang, S; Miao, Y.S.; Han, Q; Jiang, M.H.; Jin, G.Z. (1993). "Effects of (-)-stepholidine and tetrahydroberberine on high potassium-evoked contraction and calcium influx in rat artery". Zhongguo Yao Li Xue Bao. 14 (3): 235–7. PMID   8237399.