Synthesis of Novel Suramin Analogs With Anti-Proliferative Activity via FGF1 and FGFRD2 Blockade

Nuzhat Parveen; Yan-Liang Lin; Ruey-Hwang Chou; Chung-Ming Sun; Chin Yu

doi:10.3389/fchem.2021.764200

Synthesis of Novel Suramin Analogs With Anti-Proliferative Activity via FGF1 and FGFRD2 Blockade

Front Chem. 2022 Jan 3:9:764200. doi: 10.3389/fchem.2021.764200. eCollection 2021.

Authors

Nuzhat Parveen¹, Yan-Liang Lin², Ruey-Hwang Chou^{3

4

5

6}, Chung-Ming Sun^{2

7}, Chin Yu¹

Affiliations

¹ Chemistry Department, National Tsing Hua University, Hsinchu, Taiwan.
² Department of Applied Chemistry, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
³ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁴ The Ph.D. Program of Biotechnology and Biomedical Industry, China Medical University, Taichung, Taiwan.
⁵ Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
⁶ Department of Medical Laboratory and Biotechnology, Asia University, Taichung, Taiwan.
⁷ Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

A promising approach in cancer therapy is the inhibition of cell proliferation using small molecules. In this study, we report the synthesis of suramin derivatives and their applications. We used NMR spectroscopy and docking simulations to confirm binding sites and three-dimensional models of the ligand-protein complex. The WST-1 assay was used to assess cell viability and cell proliferation in vitro to evaluate the inhibition of protein-protein interactions and to investigate the anti-proliferative activities in a breast cancer cell line. All the suramin derivatives showed anti-proliferative activity by blocking FGF1 binding to its receptor FGFRD2. The dissociation constant was measured by fluorescence spectroscopy. The suramin compound derivatives synthesized herein show potential as novel therapeutic agents for their anti-proliferative activity via the inhibition of protein-protein interactions. The cytotoxicity of these suramin derivatives was lower than that of the parent suramin compound, which may be considered a significant advancement in this field. Thus, these novel suramin derivatives may be considered superior anti-metastasis molecules than those of suramin.

Keywords: FGF1; FGFRD2; NMR; WST1 assay; cell proliferation; cytotoxicity; protein-ligand interaction.