Exploring efficacy of Natural-derived Acetylphenol Scaffold Inhibitors for α-Glucosidase: synthesis, in vitro and in vivo biochemical studies.

Exploring efficacy of Natural-derived Acetylphenol Scaffold Inhibitors for α-Glucosidase: synthesis, in vitro and in vivo biochemical studies. Bioorg Med Chem Lett. 2020 Sep 10;:127528 Authors: Yu X, Zhang F, Liu T, Liu Z, Dong Q, Li D Abstract The discovery of novel α-glucosidase inhibitors and anti-diabetic candidates from natural or natural-derived products represents an attractive therapeutic option. Here, a collection of acetylphenol analogues derived from paeonol and acetophenone were synthesized and evaluated for their α-glucosidase inhibitory activity. Most of derivatives, such as 9a - 9e, 9i, 9m - 9n and 11d - 11e, (IC50 = 0.57 ± 0.01 μM to 8.45 ± 0.57 μM), exhibited higher inhibitory activity than the parent natural products and were by far more potent than the antidiabetic drug acarbose (IC50 = 57.01 ± 0.03 μM). Among these, 9e and 11d showed the most potent activity in a non-competitive manner. The binding processes between the two most potent compounds and α-glucosidase were spontaneous. Hydrophobic interactions were the main forces for the formation and stabilization of the enzyme - acetylphenol scaffold inhibitor complex, and induced the topography image changes and aggregation of α-glucosidase. In addition, everted intestinal sleeves in vitro and the maltose loading test in vivo further demonstrated the α-glucosidase inhibition of the two compounds, and our findings proved that they have significant postpr...
Source: Bioorganic and Medicinal Chemistry Letters - Category: Chemistry Authors: Tags: Bioorg Med Chem Lett Source Type: research