2. Academic Validation
  3. Design, synthesis, and biological evaluation of 1,3,6,7-tetrahydroxyxanthone derivatives as phosphoglycerate mutase 1 inhibitors

Design, synthesis, and biological evaluation of 1,3,6,7-tetrahydroxyxanthone derivatives as phosphoglycerate mutase 1 inhibitors

  • Bioorg Med Chem Lett. 2021 Mar 15:36:127820. doi: 10.1016/j.bmcl.2021.127820.
Kaixuan Jiang 1,  Biao Gao 1,  Jing Yu 1,  Lulu Jiang 2,  Ao Niu 1,  Yihe Jia 1,  Tao Meng 1,  Lu Zhou 3,  Jinxin Wang 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826, Zhangheng Rd, Shanghai 201203, China.
  • 3 Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826, Zhangheng Rd, Shanghai 201203, China. Electronic address: [email protected].
  • 4 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: [email protected].
PMID: 33513389 DOI: 10.1016/j.bmcl.2021.127820
Abstract

Phosphoglycerate mutase 1 (PGAM1) is a promising target for Cancer treatment. Herein, we found that α-mangostin and γ-mangostin exhibited moderate PGAM1 inhibitory activities, with IC50 of 7.2 μM and 1.2 µM, respectively. Based on α-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.

Keywords

1,3,6,7-Tetrahydroxyxanthone derivatives; Mangostin; PGAM1 inhibitor.

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