Design, Synthesis, and Biological Evaluation of Novel Apigenin Derivatives as Potential Antitumor Agents

Objective: The objective of this study was to design and synthesize novel apigenin derivatives and evaluate their antitumor activities against NSCLC cells. Methods: A series of apigenin derivatives were synthesized and their antiproliferative effects were evaluated against the NSCLC cell line A549. The most promising compounds were identified based on their antitumor activities. Their safety was confirmed by testing them on the normal human lung cell line Beas-2B. The mechanisms of their antitumor activities were investigated by inducing apoptosis in A549 cells and inhibiting Akt protein phosphorylation. The physicochemical and ADME properties of these compounds were also predicted to evaluate their potential as PI3K inhibitors for NSCLC therapy. Results and Discussion: Compounds (Va) and (VIa) exhibited suitable antitumor activities against A549 cells, with no significant toxicity towards Beas-2B cells. They were capable of inducing apoptosis in A549 cells and inhibiting Akt protein phosphorylation, which preliminarily revealed their mechanisms for antitumor activities in vitro. The predictions of physicochemical and ADME properties showed that compound (VIa) would be a potent PI3K inhibitor for NSCLC therapy in the future. Conclusions: This study has successfully designed and synthesized apigenin derivatives with antitumor activities for NSCLC therapy. Compounds (Va) and (VIa) exhibited suitable antitumor activities with low toxicity and promising mechanisms of action. The physicochemical and ADME properties of compound (VIa) suggest its potential as a potent PI3K inhibitor for NSCLC therapy in the future. These findings provide valuable insights for the development of novel therapeutic agents against NSCLC.