School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, P.R. China.
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):451-461. doi: 10.1080/14756366.2021.2018682.
Different oleanolic acid (OA) oxime ester derivatives (-) were designed and synthesised to develop inhibitors against -glucosidase and -amylase. All the synthesised OA derivatives were evaluated against -glucosidase and -amylase Among them, compound showed the highest -glucosidase inhibition with an IC of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound exhibited the highest -amylase inhibitory with an IC of 3.80 µM that was ∼26 times higher than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compounds and were reversible and mixed types towards -glucosidase and -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 and against 3T3-L1 and HepG2 cells.HighlightsOleanolic acid oxime ester derivatives () were synthesised and screened against α-glucosidase and α-amylase.Compound showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM.Compound presented the highest α-amylase inhibitory with IC50 of 3.80 µM.Kinetic studies and studies analysed the binding between compounds and α-glucosidase or α-amylase.
不同的齐墩果酸肟酯衍生物（）被设计和合成，以开发抑制 - 葡萄糖苷酶和 - 淀粉酶的抑制剂。所有合成的 OA 衍生物均针对 - 葡萄糖苷酶和 - 淀粉酶进行了评估。其中，化合物表现出最高的 - 葡萄糖苷酶抑制活性，IC 为 0.35µM，比阿卡波糖强约 1900 倍，同时化合物表现出最高的 - 淀粉酶抑制活性，IC 为 3.80µM，比阿卡波糖高约 26 倍。抑制动力学研究表明，化合物和对 - 葡萄糖苷酶和 - 淀粉酶的抑制机制分别为可逆和混合类型。分子对接研究分别分析了化合物与两种酶之间的相互作用。此外，细胞毒性评估试验表明化合物和对 3T3-L1 和 HepG2 细胞具有较高的安全性。
