Design and Synthesis of Novel Anti-proliferative Formononetin Derivatives

aims: aimed to synthesize and evaluate the potential antineoplastic activity of eight newly synthesized FMN derivatives background: Formononetin (FMN) is an isoflavone component of the natural product Astragalus membranaceus. Its well-documented anticancer activity led to the synthesis of new derivatives. objective: This study aimed to synthesize and evaluate the potential antineoplastic activity of eight newly synthesized FMN derivatives. method: Evaluation of the anti-tumor effects and potential mechanisms of action of derivatives using methods such as tetrazolium bromidesalt (MTT), cell cloning, EdU staining, Tunel staining, Transwell chamber , flow cytometry, and enzyme-linked immunosorbent assay (ELISA). result: As indicated by the results, all compounds exhibited toxicity to all three types of cancer cells. Most derivatives exhibited more significant antiproliferative activity than FMN. In comparison with other derivatives, compound 8 displayed the maximum antiproliferative activity, with IC50 value of 8.973 ± 0.296, 7.240 ± 0.208, and 4.378 ± 0.380 μ mol/L for HeLa, A549, and HepG2 cells, separately. In addition, further experiments demonstrated that compound 8 could suppress in vitro proliferation of HepG2 cells, promote HepG2 cell apoptosis, suppress HepG2 cell migration and invasion, and arrest HepG2 cell growth in S phase. The mechanism may be through the reduction of Bcl-2 and Mcl-1 protein expression, the increase of Bax, P53, Fas, Caspase-3 and Caspase-9 protein expression, the reduction of mitochondrial membrane potential and the reduction of ATP production, thus promoting the apoptosis of HepG2 cells. conclusion: Compound 8 may serve as a lead compound with high potential in discovering novel antitumor drugs. Furthermore, it can be explored in depth as an anticancer drug. other: none