Canadine

Bioorg Med Chem. 2008 Apr 1;16(7):3641-51.

Antioxidant and cytotoxic activities of canadine: biological effects and structural aspects.[Pubmed: 18295494]

METHODS AND RESULTS:
The cytotoxic effects of four alkaloids, berberine, Canadine, anonaine, and antioquine were evaluated using three different cell cultures, a primary culture (rat hepatocytes) and two cell lines (HepG2 and HeLa). Our results indicate that berberine, anonaine, and antioquine possess a significant the cytotoxic effect. In contrast, Canadine does not possess cytotoxic effect at concentrations tested here. A molecular modeling study indicates that the quaternary nitrogen, the aromatic polycyclic and planar structure of berberine could be the pharmacophoric patron to produce the cytotoxic effect. In parallel our results demonstrated that Canadine possess a significant antioxidant activity. Stereoelectronic aspects of this alkaloid were found to be closely related to those displayed by alpha-tocopherol and its water-soluble analogue trolox.
CONCLUSIONS:
The antioxidant activities of Canadine, combined with its low-toxic effect, indicated that the potential of this alkaloid as a novel class of antioxidant agent is very interesting and deserves further research.

FEBS Lett. 2014 Jan 3;588(1):198-204.

Cloning and characterization of canadine synthase involved in noscapine biosynthesis in opium poppy.[Pubmed: 24316226]

Noscapine biosynthesis in opium poppy is thought to occur via N-methylCanadine, which would be produced through 9-O-methylation of (S)-scoulerine, methylenedioxy bridge formation on (S)-tetrahydrocolumbamine, and N-methylation of (S)-Canadine. Only scoulerine 9-O-methyltransferase has been functionally characterized.
METHODS AND RESULTS:
We report the isolation and characterization of a cytochrome P450 (CYP719A21) from opium poppy that converts (S)-tetrahydrocolumbamine to (S)-Canadine. Recombinant CYP719A21 displayed strict substrate specificity and high affinity (Km=4.63±0.71 μM) for (S)-tetrahydrocolumbamine. Virus-induced gene silencing of CYP719A21 caused a significant increase in (S)-tetrahydrocolumbamine accumulation and a corresponding decrease in the levels of putative downstream intermediates and noscapine in opium poppy plants.