Title:Design and Synthesis of Novel Anti-proliferative Formononetin Derivatives
Volume: 21
Issue: 16
Author(s): Zeping Luo*, Liwei Pan, XiuJu Yin and Hailin Chen
Affiliation:
- Guangxi Collaborative Innovation Center of Modern Sericulture and Silk, Department of Chemistry and Bioengineering,
Hechi University, P.O. Box: 546300, Hechi, China
Keywords:
Formononetin, derivatives, anti-proliferative, cancer, anti-H. pylori, clinical applications.
Abstract:
Background: This study aimed to design and synthesize a series of novel C8-
Formononetin derivatives and evaluate their in vitro anti-tumor activity. The experimental results
showed that these derivatives exhibited varying degrees of anti-tumor effects on HeLa, A549, and
HepG2 cells, and compound 8, in particular, showed excellent inhibitory activity against HepG2 cell
growth, which surpassed that of 5-FU.
Methods: Importantly, the cytotoxicity of FMN was significantly enhanced after conjugation with
amino acid ethyl ester. To further investigate the mechanisms underlying the anti-tumor effects of
these derivatives, various experimental approaches were employed. They include colony formation
assay, EdU cell proliferation assay, Transwell migration assay, cell apoptosis assay, cell cycle distribution
assay, and ELISA.
Results: The results revealed that compound 8 effectively induced cell apoptosis by downregulating
the expression of anti-apoptotic proteins P53, Bcl-2, and Mcl-1 while upregulating the expression of
pro-apoptotic proteins Bax, Fas, Caspase-3, Caspase-9, and Fas, which leads to apoptosis of tumor
cells. Furthermore, compound 8 disrupted the mitochondrial membrane potential, perturbed cellular
energy metabolism, and reduced intracellular ATP levels, thereby inhibiting tumor cell growth.
Conclusion: The newly synthesized FMN derivatives in this study hold great potential in the field of
anti-tumor research. Compound 8 inhibits tumor cell growth through multiple pathways, which provides
new hope for cancer treatment.
