Canadine

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.

(S)-Canadine is the immediate metabolic precursor of berberine, which is produced through the action of the enzyme tetrahydroberberine oxidase.

It is also an intermediate in the biosynthesis of noscapine, which is likewise a benzylisoquinoline alkaloid, but of the phthalideisoquinoline structural subgroup.

(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. (S)-Canadine blocks K(ATP) channels in dopamine neurons. (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. (S)-Canadine can block voltage-dependent calcium channels, but at a level significantly lower than that of verapamil.

[[CPU 86017]]

Canadine is also used in the synthesis of CPU 86017 (a novel Class III antiarrhythmic agent with multiple actions at ion channels).

References

References

1. (2015). "Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants". BMC Plant Biology.
2. (2014). "CYP82Y1 is N-Methylcanadine 1-Hydroxylase, a Key Noscapine Biosynthetic Enzyme in Opium Poppy". The Journal of Biological Chemistry.
3. (2014). "Short-chain dehydrogenase/reductase catalyzing the final step of noscapine biosynthesis is localized to laticifers in opium poppy". The Plant Journal.
4. (2017). "Canadine from Corydalis turtschaninovii Stimulates Myoblast Differentiation and Protects against Myotube Atrophy". International Journal of Molecular Sciences.
5. (2010). "Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta". Neuropharmacology.
6. (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.
7. (2008). "Antioxidant and cytotoxic activities of canadine: Biological effects and structural aspects". Bioorganic & Medicinal Chemistry.
8. (2018). "Synthesis and biological evaluation of novel heteroring-annulated pyrrolino-tetrahydroberberine analogues as antioxidant agents". Bioorganic & Medicinal Chemistry.
9. (1993). "Effects of (-)-stepholidine and tetrahydroberberine on high potassium-evoked contraction and calcium influx in rat artery". Zhongguo Yao Li Xue Bao.
10. Dai, De-Zai. (2006). "CPU86017: a novel Class III antiarrhythmic agent with multiple actions at ion channels". Cardiovascular Drug Reviews.