Design, Synthesis, And Biological Evaluation Of 1,3,6,7-Tetrahydroxyxan- Thone Derivatives As Phosphoglycerate Mutase 1 Inhibitors

Phosphoglycerate mutase 1 (PGAM1) is a promising target for cancer treatment. Herein, we found that alpha-mangostin and gamma-mangostin exhibited moderate PGAM1 inhibitory activities, with IC50 of 7.2 mu M and 1.2 mu M, respectively. Based on alpha-mangostin, a series of 1,3,6,7-tetrahydroxyxanthone derivatives were designed, synthesized and evaluated in vitro for PGAM1 inhibition. The significant structure-activity relationships (SAR) and a fresh binding mode of this kind of new compounds were also clearly described. This study provides valuable information for further optimization of PGAM1 inhibitors with 1,3,6,7-tetrahydroxyxanthone backbone or de novo design of novel inhibitor.