Synthesis and bioactivities evaluation of oleanolic acid oxime ester derivatives as <i>α</i>-glucosidase and <i>α</i>-amylase inhibitors
Xu-Yang Deng, Jun-Jie Ke, Yingying Zheng, Dongli Li, Kun Zhang, Xi Zheng, Jing-Ying Wu, Zhuang Xiong, Panpan Wu, Xue-Tao Xu
Abstract
Different oleanolic acid (OA) oxime ester derivatives (<b>3a</b>-<b>3t</b>) were designed and synthesised to develop inhibitors against <i>α</i>-glucosidase and <i>α</i>-amylase. All the synthesised OA derivatives were evaluated against <i>α</i>-glucosidase and <i>α</i>-amylase <i>in vitro.</i> Among them, compound <b>3a</b> showed the highest <i>α</i>-glucosidase inhibition with an IC<sub>50</sub> of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound <b>3f</b> exhibited the highest <i>α</i>-amylase inhibitory with an IC<sub>50</sub> of 3.80 µM that was ∼26 times higher than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compounds <b>3a</b> and <b>3f</b> were reversible and mixed types towards <i>α</i>-glucosidase and <i>α</i>-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 <b>3a</b> and <b>3f</b> against 3T3-L1 and HepG2 cells.HighlightsOleanolic acid oxime ester derivatives (<b>3a–3t</b>) were synthesised and screened against α-glucosidase and α-amylase.Compound <b>3a</b> showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM.Compound <b>3f</b> presented the highest α-amylase inhibitory with IC50 of 3.80 µM.Kinetic studies and <i>in silico</i> studies analysed the binding between compounds and α-glucosidase or α-amylase. Oleanolic acid oxime ester derivatives (<b>3a–3t</b>) were synthesised and screened against α-glucosidase and α-amylase. Compound <b>3a</b> showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM. Compound <b>3f</b> presented the highest α-amylase inhibitory with IC50 of 3.80 µM. Kinetic studies and <i>in silico</i> studies analysed the binding between compounds and α-glucosidase or α-amylase.