Design, synthesis, and biological evaluation of novel urolithins derivatives as potential phosphodiesterase II inhibitors

A series of urolithins derivatives were designed and synthesized, and their structures have been confirmed by 1 H NMR, 13 C NMR, and HR-MS. The inhibitory activity of these derivatives on phosphodiesterase II (PDE2) was thoroughly studied with 3-hydroxy-8-methyl-6 H -benzo[C]chromen-6-one and 3-hydroxy-7,8,9,10-tetrahydro-6 H -benzo[C] chromen-6-one as the lead compounds. The biological activity test showed that compound 2e had the best inhibitory activity on PDE2 with an IC 50 of 33.95 μM. This study provides a foundation for further structural modification and transformation of urolithins to obtain PDE2 inhibitor small molecules with better inhibitory activity.