Synthesis and Activity Evaluation of Novel Benzoxazepinone Derivatives as Potential Inhibitors of Glycogen Phosphorylase.

ABSTRACT: Glycogen phosphorylase (GP) is a key enzyme of glycogen catabolism, so it is significant to discover a new GP inhibitor. A series of benzoxazepinone derivatives were identified as glycogen phosphorylase (GP) inhibitors with potent activity. These compounds exhibited strong inhibitory effects. Among them, compound 8g (IC₅₀ = 0.62 ± 0.16 μM) showed significant inhibitory activity against rabbit muscle glycogen phosphorylase a (GPa). Its inhibition of glycogen degradation in HL-7702 cells was three times greater than that of PSN-357. Molecular docking studies revealed that the binding conformation of compound 8g with PYGL allowed the benzoxazinone moiety to form stable hydrogen-bond networks and hydrophobic interactions, which may explain its excellent activity

SUBMITTER: Peng D 

PROVIDER: S-EPMC12608647 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature