Acetylcholinesterase Inhibitory Activity of Modified Lupane, Oleanane, and Ursane A-seco-Triterpenoids
Anastasiya V Petrova1, Oxana B Kazakova1, Ivan S Nazarov1
1Ufa Institute of Chemistry of the Ufa Federal Research Center of the, Russian Academy of Sciences, 71, prospect Octyabrya, Ufa, 450054, Russian Federation.
Abstract:
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 Ki =0.18 μM and Ki =0.21 μM, respectively.
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