Design and Synthesis of Novel Anti-proliferative Formononetin Derivatives

Zeping      Luo; Liwei      Pan; XiuJu      Yin; Hailin      Chen
doi:10.2174/0115701808278216231228045423
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.
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DOI https://dx.doi.org/10.2174/0115701808278216231228045423	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X
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