The Design and Synthesis of N-Xanthone Benzenesulfonamides as Novel Phosphoglycerate Mutase 1 (PGAM1) Inhibitors

Penghui Wang; Lulu Jiang; Yang Cao; Deyong Ye; Lu Zhou

doi:10.3390/molecules23061396

The Design and Synthesis of N-Xanthone Benzenesulfonamides as Novel Phosphoglycerate Mutase 1 (PGAM1) Inhibitors

Molecules. 2018 Jun 8;23(6):1396. doi: 10.3390/molecules23061396.

Authors

Penghui Wang¹, Lulu Jiang², Yang Cao³, Deyong Ye⁴, Lu Zhou⁵

Affiliations

¹ Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826, Zhangheng Rd., Shanghai 201203, China. wangph@fudan.edu.cn.
² Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826, Zhangheng Rd., Shanghai 201203, China. lljiang16@fudan.edu.cn.
³ Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826, Zhangheng Rd., Shanghai 201203, China. ycao14@fudan.edu.cn.
⁴ Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826, Zhangheng Rd., Shanghai 201203, China. dyye@shmu.edu.cn.
⁵ Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826, Zhangheng Rd., Shanghai 201203, China. zhoulu@fudan.edu.cn.

Abstract

Upregulation of phosphoglycerate mutase 1 (PGAM1) has been identified as one common phenomenon in a variety of cancers. Inhibition of PGAM1 provides a new promising therapeutic strategy for cancer treatment. Herein, based on our previous work, a series of new N-xanthone benzenesulfonamides were discovered as novel PGAM1 inhibitors. The representative molecule 15h, with an IC₅₀ of 2.1 μM, showed an enhanced PGAM1 inhibitory activity and higher enzyme inhibitory specificity compared to PGMI-004A, as well as a slightly improved antiproliferative activity.

Keywords: anti-cancer; inhibitors; phosphoglycerate mutase 1; xanthone.

MeSH terms

Benzenesulfonamides
Carbon-13 Magnetic Resonance Spectroscopy
Cell Line
Cell Proliferation / drug effects
Drug Design*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Phosphoglycerate Mutase / antagonists & inhibitors*
Proton Magnetic Resonance Spectroscopy
Spectrometry, Mass, Electrospray Ionization
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / pharmacology*
Xanthones / chemistry*

Substances

Enzyme Inhibitors
Sulfonamides
Xanthones
Phosphoglycerate Mutase
phosphoglycerate mutase 1, human