Acetylcholinesterase Inhibitory Activity of Modified Lupane, Oleanane, and Ursane A-seco-Triterpenoids

A series of new lupane, ursane, and oleanane type triterpenic A-seco-derivatives containing bromo-, azido-, alkyne-, 1H-tetrazol-5-yl-, 5-methyloxazol-2-yl-, N-(4-(4-methylpiperazin-1-yl)but-2-yn-1-yl), and a carbonyl group at C2, C24, C28, C30 positions has been synthesized. The bioactivity was evaluated by Ellman's method, and the results showed that most of the compounds displayed moderate acetylcholinesterase inhibitory activities in vitro. Among them, A-seco-derivatives of 28-oxo-allobetuline and betulinic acid with bromo- and azido-groups exhibited the most potent inhibitory activity against AChE. Extra experiments showed methyl 2-cyano-3,4-seco-dibromo- and 2-cyano-3,4-seco-diazido-derivatives of betulinic acid as mixed-type inhibitors, with Ki values as low as K-i=0.18 mu M and K-i=0.21 mu M, respectively.

Automated summary

A series of new lupane, ursane, and oleanane type triterpenic A-seco-derivatives containing various functional groups have been synthesized and evaluated for their acetylcholinesterase inhibitory activities. The results showed that the bromo- and azido-derivatives of 28-oxo-allobetuline and betulinic acid exhibited the most potent inhibitory activity against AChE. Further experiments demonstrated the cyano-derivatives of betulinic acid as mixed-type inhibitors with low Ki values.