Synthesis and bioactivities evaluation of oleanolic acid oxime ester derivatives as α-glucosidase and α-amylase inhibitors. (31st December 2022)

• Record Type: Journal Article
• Authors: Deng, Xu-Yang; Ke, Jun-Jie; Zheng, Ying-Ying; Li, Dong-Li; Zhang, Kun; Zheng, Xi; Wu, Jing-Ying; Xiong, Zhuang; Wu, Pan-Pan; Xu, Xue-Tao
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 37:Number 1(2022)
• Page Start: 451
• Page End: 461
• Publication Date: 2022-12-31
• Subjects: Oleanolic acid -- structural modification -- α-glucosidase -- α-amylase -- enzyme inhibition; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2021.2018682
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: 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. Highlights: Oleanolic 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. Graphical abstract: UF0001