Design, Synthesis, and Biological Evaluation of Novel 6H-Benzo[c]chromen-6-one Derivatives as Potential Phosphodiesterase II Inhibitors
Long Tang, Jianchun Jiang, Guoqiang Song, Yajing Wang, Ziheng Zhuang, Ying Tan, Yan Xia, Xianfeng Huang, Xiaoqing Feng
Abstract
Urolithins (hydroxylated 6H-benzo[c]chromen-6-ones) are the main bioavailable metabolites of ellagic acid (EA), which was shown to be a cognitive enhancer in the treatment of neurodegenerative diseases. As part of this research, a series of alkoxylated 6H-benzo[c]chromen-6-one derivatives were designed and synthesized. Furthermore, their biological activities were evaluated as potential PDE2 inhibitors, and the alkoxylated 6H-benzo[c]chromen-6-one derivative 1f was found to have the optimal inhibitory potential (IC50: 3.67 ± 0.47 μM). It also exhibited comparable activity in comparison to that of BAY 60-7550 in vitro cell level studies.