Xanthone derivatives as phosphoglycerate mutase 1 inhibitors: Design, synthesis, and biological evaluation
- Bioorg Med Chem. 2018 May 1;26(8):1961-1970. doi: 10.1016/j.bmc.2018.02.044.
- 1. Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No.826, Zhangheng Rd, Shanghai 201203, China.
- 2. Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No.826, Zhangheng Rd, Shanghai 201203, China. Electronic address: [email protected].
- 3. Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No.826, Zhangheng Rd, Shanghai 201203, China. Electronic address: [email protected].
Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that dynamically converts 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG), which was upregulated to coordinate glycolysis, pentose phosphate pathway (PPP) and serine biosynthesis to promote Cancer cell proliferation and tumor growth in a variety of cancers. However, only a few inhibitors of PGAM1 have been reported with poor molecular or cellular efficacy. In this paper, a series of xanthone derivatives were discovered as novel PGAM1 inhibitors through scaffold hopping and sulfonamide reversal strategy based on the lead compound PGMI-004A. Most xanthone derivatives showed higher potency against PGAM1 than PGMI-004A and exhibited moderate anti-proliferation activity on different Cancer cell lines.