AUTHOR=Parveen Nuzhat , Lin Yan-Liang , Chou Ruey-Hwang , Sun Chung-Ming , Yu Chin
TITLE=Synthesis of Novel Suramin Analogs With Anti-Proliferative Activity via FGF1 and FGFRD2 Blockade
JOURNAL=Frontiers in Chemistry
VOLUME=9
YEAR=2022
URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.764200
DOI=10.3389/fchem.2021.764200
ISSN=2296-2646
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.