Highly efficient synthesis and monoamine oxidase B inhibitory profile of demethyleneberberine, columbamine and palmatine

• Published in: Neurochemistry international 2020-10, Vol.139, p.104807, Article 104807
• Main Authors: Tao, Cheng, Hu, Sheng-quan, Chen, Jian, Chen, Yuan-ji, Sun, Ke-huan, Cui, Guo-zhen, Ma, Min, Wu, Zheng-zhi
• Format: Article
• Language: English
• Subjects: Columbamine; Demethyleneberberine; Monoamine oxidase B; Reversibility
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2020.104807

The biosynthesis of berberine alkaloids is thought to begin with the demethylation of berberine followed by methylation reactions to generate other type berberine alkaloids. This seemingly expeditious way to access berberine alkaloids has been stagnated for over half a century due to certain vexing synthetic problems, such as low isolated yield, complex operations and toxic reagents. We further investigated this bioinspired semi-synthesis strategy and significantly improved the synthetic efficacy, by providing a practical synthetic process for demethyleneberberine (DMB), columbamine and palmatine. Furthermore, we found that DMB (IC50, 9.06 μM) inhibited the activity of monoamine oxidase B (MAO-B), an enzyme that deaminates dopamine and is particularly involved in the pathology of Parkinson's disease. Besides, columbamine was able to decrease MAO-B activity by approximately 40%. These findings provide perquisites for further in vivo investigation to confirm the therapeutic potentiality of berberine alkaloids, DMB in particular. [Display omitted] •An effective and practical semi-synthetic procedure of demethyleneberberine, columbamine and palmatine has been developed.•Demethyleneberberine (IC50, 9.06 μM) inhibited the activity of monoamine oxidase B (MAO-B).•Our work would provide valuable insight for the semi-synthesis and pharmacological studies of berberine alkaloids.