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

Different oleanolic acid (OA) oxime ester derivatives ( 3a - 3t ) were designed and synthesised to develop inhibitors against α -glucosidase and α -amylase. All the synthesised OA derivatives were evaluated against α -glucosidase and α -amylase in vitro. Among them, compound 3a showed the highest α -glucosidase inhibition with an IC 50 of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound 3f exhibited the highest α -amylase inhibitory with an IC 50 of 3.80 µM that was ∼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 α -glucosidase and α -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.HighlightsOleanolic acid oxime ester derivatives ( 3a-3t ) were synthesised and screened against α-glucosidase and α-amylase.Compound 3a showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM.Compound 3f presented the highest α-amylase inhibitory with IC50 of 3.80 µM.Kinetic studies and in silico studies analysed the binding between compounds and α-glucosidase or α-amylase.