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

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 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. 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.

Inhibitory Potential of α-Amylase, α-Glucosidase, and Pancreatic Lipase by a Formulation of Five Plant Extracts: TOTUM-63

“…For instance, cyanidin (one of TOTUM-63 anthocyanins), apigenin, luteolin-7-O-glucoside, and oleanolic acid exert strong inhibitory effects on α-glucosidase [ 45 , 46 , 47 , 48 ]. Oleanolic acid showed the strongest effect with 162 times higher inhibitory activities on α-glucosidase compared with acarbose (IC 50 = 4.09 µM for oleanolic acid and IC 50 = 665.56 µM for acarbose) [ 49 ]. Moreover, other studies have demonstrated major or minor inhibitory effects on α-glucosidase for several other compounds identified in TOTUM-63: apigenin-7-O-glucuronide, dicaffeoylquinic acids (including cynarin), eriodictyol, marein, flavanomarein, and apigenin-6,8-C-diglucoside (vicenin 2) [ 50 , 51 , 52 , 53 , 54 ].…”

Synthesis and Biological Evaluation of 5-Fluoro-2-Oxindole Derivatives as Potential α-Glucosidase Inhibitors

“…The α-glucosidase inhibition of synthetic compounds was performed as previously reported methods with minor modification ( Deng et al, 2022 ) which is as follows: briefly, 130 μl of phosphate buffer (10 mM, pH 6.8), 10 μl of α-glucosidase (1 U/ml), and 10 μl of test compound solution were added into the wells of a 96-well plate, followed by incubation for 10 min at 37°C. Then, 50 μl of p -NPG (1 mM) was added, and the plate was further incubated for 30 min at 37°C.…”

Exogenous additives facilitate the fermentation of cigar tobacco leaves: improving sensory quality and contents of aroma components

“…Characteristics of mellowness, matureness, and smoothness of CTLs were improved obviously. The addition of α-amylase could promote the production of polysaccharide effectively, thus improving the sweetness of CTLs (Deng et al, 2022). However, thickened protein odor with the addition of three enzymes could not be ignored, which may be caused by the excessive addition amount of enzyme.…”