α-Glucosidase and cholinesterase inhibiting potential of a series of semisynthetic nitrogen triterpenic derivatives

In this study, a series of 40 semisynthetic nitrogen triterpenic derivatives of lupane, oleanane and ursane type including 33 previously synthesized and 7 new compounds were synthesized and screened to determine their ability to act as inhibitors for the enzymes alpha-glucosidase (from S. saccharomyces), acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). As a result, 17 out of 40 compounds demonstrated significant inhibitory properties toward alpha-glucosidase with IC50 values not exceeding 10 mu M with IC50 178.25 mu M for acarbose as a reference. A-azepano-28-cinnamoyloxy-erythrodiol was found as a lead compound holding an IC50 value of 0.22 mu M, and thus being 810 times more active than acarbose. Compounds 6 and 15 were moderate inhibitors for the enzyme AChE but less active for BChE, lupane type amidoxime 11 exhibited a higher activity with 41.98% inhibition of AChE, while ursonic acid N-ethyl-piperazinyl-amide 34 was an inhibitor for BChE holding an inhibition value of 65.60%, which was better than the reference drug galantamine hydrobromide. Thus, we have revealed new triterpenic derivatives with promising enzyme inhibitory activity. [GRAPHICS]