Portal de Periódicos da CAPES

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

2022; Taylor & Francis; Volume: 37; Issue: 1 Linguagem: Inglês

10.1080/14756366.2021.2018682

1475-6374

Xu-Yang Deng, Jun-Jie Ke, Yingying Zheng, Dongli Li, Kun Zhang, Xi Zheng, Jing-Ying Wu, Zhuang Xiong, Panpan Wu, Xue-Tao Xu,

Natural product bioactivities and synthesis

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 IC50 of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound 3f exhibited the highest α-amylase inhibitory with an IC50 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.