Zhen Jing, Dai Yujie, Villani Tom, Giurleo Daniel, Simon James E, Wu Qingli
The New Use Agriculture and Natural Plant Products Program, Department of Plant Biology, Rutgers University, 59 Dudley Road, New Brunswick, NJ 08901, USA; Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers University, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Key Laboratory of Industrial Fermentation Microbiology, Tianjin University of Science and Technology, Tianjin 300457, China.
Bioorg Med Chem. 2017 Oct 15;25(20):5355-5364. doi: 10.1016/j.bmc.2017.07.055. Epub 2017 Jul 29.
A series of novel flavonoid alkaloids were synthesized with different flavonoids and attached nitrogen-containing moieties. These new compounds were screened for inhibitory activity of α-glucosidase, among which compound 23 was found to show the lowest IC of 4.13μM. Kinetic analysis indicates that the synthesized compounds 15 and 23 inhibit the enzyme in a non-competitive model with Ki value of 37.8±0.8μM and 13.2±0.6μM. Further docking studies suggest that the preferred binding pocket is close to the catalytic center, correlating to the experimental results. Structure activity relationship studies (SAR) indicate that 4'-hyroxyl group and the 4-position carbonyl group in the flavonoid structure are important for this biological activity. Addition of extra hydrogen bonding and hydrophobic groups on ring A would increase the inhibitory activity.
一系列新型黄酮类生物碱通过不同的黄酮类化合物与含氮部分合成。对这些新化合物进行了α-葡萄糖苷酶抑制活性筛选，其中化合物23的IC50最低，为4.13μM。动力学分析表明，合成的化合物15和23以非竞争性模式抑制该酶，Ki值分别为37.8±0.8μM和13.2±0.6μM。进一步的对接研究表明，优选的结合口袋靠近催化中心，与实验结果相关。构效关系研究（SAR）表明，黄酮类结构中的4'-羟基和4-位羰基对这种生物活性很重要。在A环上添加额外的氢键和疏水基团会增加抑制活性。
