2. Academic Validation
  3. Xanthone derivatives as phosphoglycerate mutase 1 inhibitors: Design, synthesis, and biological evaluation

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.
Penghui Wang 1,  Lulu Jiang 1,  Yang Cao 1,  Xiaodan Zhang 1,  Bangjing Chen 1,  Shiyu Zhang 1,  Ke Huang 1,  Deyong Ye 2,  Lu Zhou 3
Affiliations

Affiliations

  • 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: dyye@shmu.edu.cn.
  • 3 Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No.826, Zhangheng Rd, Shanghai 201203, China. Electronic address: zhoulu@shmu.edu.cn.
PMID: 29530347 DOI: 10.1016/j.bmc.2018.02.044
Abstract

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.

Keywords

Cancer cell metabolism; Inhibitors; Phosphoglycerate mutase 1; Xanthone derivatives.

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