Discovery and characterization of naturally occurring potent inhibitors of catechol-<i>O</i>-methyltransferase from herbal medicines
Dongfang Zhao, Yufan Fan, Fangyuan Wang, Fan-Bin Hou, Frank J. Gonzalez, Shi-Yang Li, Ping Wang, Yangliu Xia, Guang‐Bo Ge, Ling Yang
Abstract
values (32.9 ± 3.43 nM, 37.3 ± 4.32 nM and 18.3 ± 2.96 nM). The results of inhibition kinetics assays and docking simulations showed that compounds 2, 9 and 12 were potent competitive inhibitors against COMT-mediated 3-BTD methylation, and they could stably bind to the active site of COMT. These findings suggested that affinity ultrafiltration allows a rapid identification of natural COMT inhibitors from a complex plant extract matrix. Furthermore, scutellarein 2, baicalein 9 and oroxylin A 12 are potent inhibitors of hCOMT in SR, which could be used as promising lead compounds to develop more efficacious non-nitrocatechol COMT inhibitors for biomedical applications.