New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity.

Abstract

BACKGROUND/AIMS:

Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1) and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2), along with five known, macusine B (3), vinorine (4), undulifoline (5), isoresrpiline (6) and rescinnamine (7) were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme.

CONCLUSION:

Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations.

• Authors: Mehran Fadaeinasab, Alireza Basiri, Yalda Kia, Hamed Karimian, Hapipah Mohd Ali, Vikneswaran Murugaiyah
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 37 Issue 5 Pg. 1997-2011 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 26584298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-beta-carboline
• Carbolines
• Indole Alkaloids
• rauvolfine C
• Acetylcholinesterase
• Butyrylcholinesterase

Topics

• Acetylcholinesterase (chemistry, metabolism)
• Binding Sites
• Butyrylcholinesterase (chemistry, metabolism)
• Carbolines
• Indole Alkaloids (chemistry, isolation & purification, metabolism)
• Inhibitory Concentration 50
• Magnetic Resonance Spectroscopy
• Molecular Docking Simulation
• Plant Bark (chemistry, metabolism)
• Protein Structure, Tertiary
• Rauwolfia (chemistry, metabolism)