Synthesis and bioactivities evaluation of oleanolic acid oxime ester derivatives as α-glucosidase and α-amylase inhibitors

Different oleanolic add (OA) oxime ester derivatives (3a-3t) were designed and synthesised to develop inhibitors against alpha-glucosidase and 7 amylase. An the synthesised OA derivatives were evaluated against alpha-glucosidase and a-amylase in vitro. Among them, compound 3a showed the highest alpha-glucosidase inhibition with an IC(50 )of 0.35 mu M, which was, similar to 1900 times stronger than that of acarbose, meanwhile compound 3f exhibited the highest 2-amylase inhibitory with an IC50 of 3.80 mu M that was similar to 26 times higher than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compounds 3a and 3f were reversible and mixed types towards alpha-glucosidase and alpha-amylase, respectively. Molecular docking studies analysed the interaction between compound and two enzymes, respectively. Furthermore, cytotoxicity evaluation assay demonstrated a high level of safety profile of compounds 3a and 3f against 3T3-L1 and HepG2 cells.

Automated summary

Different oleanolic add (OA) oxime ester derivatives were designed and synthesised to develop inhibitors against alpha-glucosidase and 7 amylase. Compound 3a showed the highest alpha-glucosidase inhibition, while compound 3f exhibited the highest alpha-amylase inhibitory. Both compounds showed a good safety profile against cells.