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.