canadine
{{chembox
| ImageFile = Canadine structure.svg
| ImageSize =
| IUPACName = 9,10-Dimethoxy-2′H-[1,3]dioxolo[4′,5′:2,3]berbine
| SystematicName = (13aS)-9,10-Dimethoxy-5,8,13,13a-tetrahydro-2H,6H-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinoline
| OtherNames = (S)-Tetrahydroberberine; Xanthopuccine
|Section1={{Chembox Identifiers
| ChemSpiderID = 19910
| StdInChI = 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
| StdInChIKey = VZTUIEROBZXUFA-INIZCTEOSA-N
| CASNo = 522-97-4
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = V2SSH085X8
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C03329
| KEGG2 = C11818
| PubChem = 21171
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 490533
| SMILES = O1c2c(OC1)cc3c(c2)CCN5[C@H]3Cc4ccc(OC)c(OC)c4C5
}}
|Section2={{Chembox Properties
| C=20 | H=21 | N=1 | O=4
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
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|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
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(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.
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.{{Cite journal|last1=Hagel|first1=Jillian M.|last2=Morris|first2=Jeremy S.|last3=Lee|first3=Eun-Jeong|last4=Desgagne-Penix|first4=Isabel|last5=Bross|first5=Crystal D.|last6=Chang|first6=Limei|last7=Chen|first7=Xue|last8=Farrow|first8=Scott C.|last9=Zhang|first9=Ye|date=2015|title=Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants|journal=BMC Plant Biology|volume=15|pages=227|doi=10.1186/s12870-015-0596-0|pmid=26384972|pmc=4575454 |doi-access=free }}
(S)-Canadine is the immediate metabolic precursor of berberine, which is obtained through the action of the enzyme (S)-tetrahydroprotoberberine oxidase. It is also an intermediate in the complex biosynthesis of noscapine, which is likewise a benzylisoquinoline alkaloid, but of the phthalideisoquinoline structural subgroup.{{Cite journal|last1=Dang|first1=Thu-Thuy T.|last2=Facchini|first2=Peter J.|date=2014|title=CYP82Y1 is N-Methylcanadine 1-Hydroxylase, a Key Noscapine Biosynthetic Enzyme in Opium Poppy|url=http://www.jbc.org/content/289/4/2013.full.pdf|journal=The Journal of Biological Chemistry|volume=289|issue=4|pages=2013–2026|doi=10.1074/jbc.M113.505099|pmid=24324259|pmc=3900951|doi-access=free}}{{Cite journal|last1=Chen|first1=Xue|last2=Facchini|first2=Peter J.|date=2014|title=Short-chain dehydrogenase/reductase catalyzing the final step of noscapine biosynthesis is localized to laticifers in opium poppy|journal=The Plant Journal|volume=77|issue=2|pages=173–184|doi=10.1111/tpj.12379|pmid=24708518|doi-access=free}}
(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.{{Cite journal|last1=Lee|first1=Hyejin|last2=Lee|first2=Sang-Jin|last3=Bae|first3=Gyu-Un|last4=Baek|first4=Nam-In|last5=Ryu|first5=Jae-Ha|date=2017|title=Canadine from Corydalis turtschaninovii Stimulates Myoblast Differentiation and Protects against Myotube Atrophy|journal= International Journal of Molecular Sciences|volume=18|issue=12|pages=2748|doi=10.3390/ijms18122748|pmid=29258243|pmc=5751347|doi-access=free}} (S)-Canadine blocks K(ATP) channels in dopamine neurons.{{Cite journal|last1=Wu|first1=Chen|last2=Yang|first2=Kechun|last3=Liu|first3=Qiang|last4=Wakui|first4=Matoko|last5=Jin|first5=Guo-zhang|last6=Zhen|first6=Xuechu|last7=Wu|first7=Jie|date=2010|title=Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta|journal=Neuropharmacology|volume=59|issue=7–8|pages=567–72|doi=10.1016/j.neuropharm.2010.08.018|pmid=20804776|s2cid=27386799}}{{Cite journal|last1=Wu|first1=Jie|last2=Jin|first2=Guo Zhang|date=1997|title=Tetrahydroberberine blocks membrane K+ channels underlying its inhibition of intracellular message-mediated outward currents in acutely dissociated CA1 neurons from rat hippocampus|journal= Brain Research|volume=775|issue=1–2|pages=214–8|doi=10.1016/s0006-8993(97)00960-8|pmid=9439847|s2cid=42250453}} (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.{{cite journal|last1=Correché|first1=Estela R.|last2=Andujar|first2=Sebastian A.|last3=Kurdelas|first3=Rita R.|last4=Lechón|first4=María J. Gómez|last5=Freile|first5=Mónica L.|last6=Enriz|first6=Ricardo D.|year=2008|title=Antioxidant and cytotoxic activities of canadine: Biological effects and structural aspects|journal=Bioorganic & Medicinal Chemistry|volume=16|issue=7|pages=3641–51|doi=10.1016/j.bmc.2008.02.015|pmid=18295494}}{{Cite journal|last1=Mari|first1=Giacomo|last2=Catalani|first2=Simona|last3=Antonini|first3=Elena|last4=De Crescentini|first4=Lucia|last5=Mantellini|first5=Fabio|last6=Santeusanio|first6=Stefania|last7=Lombardi|first7=Paolo|last8=Amicucci|first8=Antonella|last9=Battistelli|first9=Serafina|date=2018|title=Synthesis and biological evaluation of novel heteroring-annulated pyrrolino-tetrahydroberberine analogues as antioxidant agents|journal= Bioorganic & Medicinal Chemistry|volume=26|issue=18|pages=5037–44|doi=10.1016/j.bmc.2018.08.038|pmid=30196978|s2cid=52177815 }} (S)-Canadine can block voltage-dependent calcium channels, but at a level significantly lower than that of verapamil.{{Cite journal|last1=Yang|first1=S|last2=Miao|first2=Y.S.|last3=Han|first3=Q|last4=Jiang|first4=M.H.|last5=Jin|first5=G.Z.|date=1993|title=Effects of (-)-stepholidine and tetrahydroberberine on high potassium-evoked contraction and calcium influx in rat artery|url=http://www.chinaphar.com/article/view/8753/9357|journal= Zhongguo Yao Li Xue Bao |volume=14|issue=3|pages=235–7|pmid=8237399}}
References
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{{Calcium channel blockers}}
Category:Calcium channel blockers