Chemistry:Canadine
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.[1]
(S)-Canadine is the immediate metabolic precursor of berberine, which is produced through the action of the enzyme tetrahydroberberine oxidase.[1]
It is also an intermediate in the 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.[4] In Corydalis cava, the enzyme berberine reductase converts berberine back to canadine but as the (R) enantiomer of the product.[5]
This type of inversion of stereochemistry allows both enantiomers of some alkaloids to be present in this species.[6]
Effects
A number of in vitro effects of (S)-canadine have been reported. It stimulates myogenesis and inhibits muscle protein degradation.[7] (S)-Canadine blocks K(ATP) channels in dopamine neurons.[8][9] (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.[10][11] (S)-Canadine can block voltage-dependent calcium channels, but at a level significantly lower than that of verapamil.[12]
CPU 86017
Canadine is also used in the synthesis of CPU 86017 (a novel Class III antiarrhythmic agent with multiple actions at ion channels).[13]
References
- ↑ 1.0 1.1 Hagel, Jillian M.; Morris, Jeremy S.; Lee, Eun-Jeong; Desgagne-Penix, Isabel; Bross, Crystal D.; Chang, Limei; Chen, Xue; Farrow, Scott C. et al. (2015). "Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants". BMC Plant Biology 15 (1): 227. doi:10.1186/s12870-015-0596-0. PMID 26384972. Bibcode: 2015BMCPB..15..227H.
- ↑ Dang, Thu-Thuy T.; Facchini, Peter J. (2014). "CYP82Y1 is N-Methylcanadine 1-Hydroxylase, a Key Noscapine Biosynthetic Enzyme in Opium Poppy". The Journal of Biological Chemistry 289 (4): 2013–2026. doi:10.1074/jbc.M113.505099. PMID 24324259. PMC 3900951. http://www.jbc.org/content/289/4/2013.full.pdf.
- ↑ 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. Bibcode: 2014PlJ....77..173C.
- ↑ "Chemical comparison of goldenseal (Hydrastis canadensis L.) root powder from three commercial suppliers". Journal of Agricultural and Food Chemistry 51 (25): 7352–8. December 2003. doi:10.1021/jf034339r. PMID 14640583. Bibcode: 2003JAFC...51.7352W.
- ↑ "Formation of (R)-configurated tetrahydroprotoberberine alkaloids in vivo and in vitro". Tetrahedron Lett. 32 (4): 487–490. 1991. doi:10.1016/S0040-4039(00)79475-5.
- ↑ Bitchagno, Gabin Thierry M.; Nchiozem-Ngnitedem, Vaderament-A.; Melchert, Dennis; Fobofou, Serge Alain (2022). "Demystifying racemic natural products in the homochiral world". Nature Reviews Chemistry 6 (11): 806–822. doi:10.1038/s41570-022-00431-4.
- ↑ 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. PMID 29258243.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Mari, Giacomo; Catalani, Simona; Antonini, Elena; De Crescentini, Lucia; Mantellini, Fabio; Santeusanio, Stefania; Lombardi, Paolo; Amicucci, Antonella et al. (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.
- ↑ 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. http://www.chinaphar.com/article/view/8753/9357.
- ↑ Dai, De-Zai (2006). "CPU86017: a novel Class III antiarrhythmic agent with multiple actions at ion channels". Cardiovascular Drug Reviews 24 (2): 101–115. doi:10.1111/j.1527-3466.2006.00101.x. ISSN 0897-5957. PMID 16961724.
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