Design, isolation, synthesis, and mechanistic insight of flavonoids isolated from Beilschmiedia obscura, as potential α-glucosidase inhibitors

Abstract

Flavonoids based on the flavone 1–3 and a biflavanoid 4 with a flavan nucleus were isolated from Beilschmiedia obscura (Stapf). These compounds which include 5- hydroxy - 7,8-dimethoxyflavanone (5), (2 S,4 R)-5, 6,7-trimethoxyflavan-4-ol (6), beilschmieflavonoid B (7), (2 R,3 S)-5,6,7-trimethoxyflavan-3-ol (8), as well as pipyahyine (9), (E,E)-1,6-bis(4-hydroxy-3-methoxyphenyl) hexa-1,5-diene-3,4-dione (10), β-sitosterol (11), pentadecanoic acid (12), pentadecan-1-ol (13), stearic acid (14) and docosane-1,2,4-triol (15), were evaluated as α-glucosidase inhibitors. The most abundant compound 5, was structurally modified by acetylation to compound 16 and NaBH4 reduction to compound 17 which represent two new derivatives of this compound class. These compounds 5–10, 16–17 including kaempferol 18, and epicatechin 19 were screened for α-glucosidase from Bacillus stearothermophyllus and showed good inhibitory activity with IC50 values = (30.55±0.12, 31.8±0.12, 32.47±0.17, 46.53±0.16, 36.43±0.12, 33, 48±0,12, 32.63±0.11 and 43.31±0.12 µM respectively) compared to acarbose (IC50 = 63.77±0.08 µM) as reference drug. Molecular docking and SAR studies further confirmed the plausible binding interactions between the flavonoids and the enzyme α-glucosidase. The results show that these compounds bind effectively to the active site of the protein X-ray structure 3wy1, which is in accordance of the observed α-glucosidase inhibitory activity.