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 enzymesα-glucosidase (fromS. saccharomyces), acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). As a result, 17 out of 40 compounds demonstrated significant inhibitory properties towardα-glucosidase with IC50 values not exceeding 10  μM with IC50 178.25  µM for acarbose as a reference. A-azepano-28-cinnamoyloxy-erythrodiol was found as a lead compound holding an IC50 value of 0.22  μM, and thus being 810 times more active than acarbose. Compounds6 and15 were moderate inhibitors for the enzyme AChE but less active for BChE, lupane type amidoxime11 exhibited a higher activity with 41.98% inhibition of AChE, while ursonic acidN-ethyl-piperazinyl-amide34 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.Graphical abstract

Source: Medicinal Chemistry Research - January 19, 2023 Category: Chemistry Source Type: research