Synthesis and Evaluation of a Series of Oleanolic Acid Saponins as α‐Glucosidase and α‐Amylase Inhibitors

Abstract

Sixteen naturally occurring oleanolic acid saponins and their derivatives were synthesized in an efficient and practical strategy, and their inhibitory activities against α-glucosidase and α-amylase were evaluated in vitro. Among all the compounds, 28-O-monoglucoside 8 exhibited remarkably potent inhibitory activity against α-glucosidase with an IC50 value of 87.3 µM, which was fivefold stronger than that of the antidiabetic acarbose. Based on the preliminary structure-activity relationships, for 28-O-monoglucosides, the presence of a terminal α-l-rhamnopyranosyl residue enhanced the α-glucosidase and α-amylase inhibitory activities. Furthermore, for 3,28-O-bidesmosides, sugar-substituted moieties attached to the C-3 and C-28 positions of the oleanolic acid scaffold are helpful to increase the inhibitory activities against α-amylase and α-glucosidase.

Machine Learning and In Vitro Chemical Screening of Potential α-Amylase and α-Glucosidase Inhibitors from Thai Indigenous Plants

“…Saponins are triterpene glycosidesbased structures, which are widely distributed in the plant as an active foamy agent. The glycone structures of saponins, especially 28-O-monosides and 3,28-O-bidesmosides, were reported to be contributed to the inhibition of α-glucosidase activity [18]. However, our study showed that a high amount of saponins were less correlated to the inhibition of the α-glucosidase enzyme.…”

“…The plants or natural products contain several active compounds against postprandial hyperglycemia [16]. Plant polyphenols (e.g., flavonoids, xanthones, tannic acids) can exhibit the anti-α-amylase and anti-α-glucosidase enzymes, which result in a reduction of the postprandial hyperglycemia [10,11,[17][18][19][20]. Traditional Thai medicines (TTM) have long been used over decades for the treatment of diabetes mellitus [21].…”

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

“…We did not find any previous studies on α-glucosidase inhibition by chrysanthellin B. However, the effects of other molecules from the same sub-families (saponins based on oleanolic acid or oleanane) on this enzyme have been studied and the reported IC 50 values were close to those of acarbose [ 43 , 44 ]. In addition, chlorogenic acid, luteolin, oleuropein, chrysanthellin B, and piperine are precursors or derivatives of several other compounds identified in TOTUM-63 (see Table 2 ) that could also potentially contribute to α-glucosidase inhibition.…”

Synthesis of furostanol glycosides: discovery of a potent α-glucosidase inhibitor

“…This result is consistent with the results reported by Bai and co-workers. 41 The sugar moiety at 4″-OH has a marginal contribution to the activity because protodioscin 4, pallidifloside I 5, coreajaponins A 6, and parisaponin I 7 could similarly inhibit α-glucosidase. To the best of our knowledge, this is the first report on the inhibitory activity of furostanol saponins against α-glucosidase, and…”