School of Chemistry & Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, PR China.
Eur J Med Chem. 2011 Sep;46(9):4050-5. doi: 10.1016/j.ejmech.2011.06.003. Epub 2011 Jun 12.
A series of novel xanthone derivatives 6-16 having non-coplanar and flexible structures were synthesized as potent α-glucosidase inhibitors. Biological evaluation indicated that compounds 6-12 bearing one or two naphthol moieties exhibited up to 30-fold enhanced activities compared with their corresponding parent compounds 2-5, whereas compounds 13-16 bearing one dihydroxylnaphthalenyl group showed decreased activities compared with their corresponding analogs 6-9 having one naphthol group. Among them, compounds 7-8, 10-12 and 15 were more active than 1-deoxynojirimycin, a well-known inhibitor for α-glucosidase. The structure-activity correlations suggested that inhibiting of α-glucosidase was a result of multiple interactions with the enzyme, including π-stacking, hydrophobic effect and conformational flexibility due to the structural non-coplanarity. In addition, compounds 4, 8 and 15 showed non-competitive inhibition.
一系列具有非共面和柔性结构的新型黄烷酮衍生物 6-16 被合成为有效的α-葡萄糖苷酶抑制剂。生物评价表明，与相应的母体化合物 2-5 相比，带有一个或两个萘酚部分的化合物 6-12 的活性增强了高达 30 倍，而带有一个二羟基萘基部分的化合物 13-16 的活性则低于相应的带有一个萘酚部分的类似物 6-9。其中，化合物 7-8、10-12 和 15 的活性比α-葡萄糖苷酶的已知抑制剂 1-去氧野尻霉素更强。结构-活性关系表明，α-葡萄糖苷酶的抑制是与酶的多种相互作用的结果，包括π堆积、疏水性和由于结构的非共面性而导致的构象灵活性。此外，化合物 4、8 和 15 表现出非竞争性抑制。
