Introduction: Lung cancer, especially Non-Small Cell Lung Carcinoma (NSCLC), is one of the deadliest malignancies globally. Current therapeutic intervention approaches often cause serious side effects and are not sufficiently effective; thus, there is a renewed academic interest in naturally bioactive compounds such as flavonoids. These phytochemicals are polyphenols that have shown significant potential in oncologic therapy due to their antioxidant, antiinflammatory, and anti-proliferative abilities. Methods: The literature review was conducted using extensive databases, including PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar. The articles chosen were those published in English over the recent years that focused on the design, synthesis, and biological evaluation of flavonoid derivatives with reference to lung cancer therapeutics. Important inclusion criteria included the studies with original data and applicability to the treatment paradigms of NSCLC. Results: Artificial flavonoid derivatives, including artificially produced chalcones, apigenin, baicalein, and triazole analogues, were all shown to have a strong cytotoxic effect on A549 lung cancer cells. These compounds were found to have low micromolar IC 50 values and exceed the effectiveness of many traditional pharmacological agents. The most effective ones triggered apoptosis, cell-cycle arrest, reduced angiogenesis, reduced inflammation, and prevented metastatic progression. Discussion: The flavonoid derivatives have an impact on various cancer-related signalling pathways, such as PI3K/Akt, NF -4, and p53. Their favourable safety profile and structural adaptability make them useful candidates for future pharmacological development. However, there are still complications in improving their pharmacokinetic properties to use them in therapeutics. Conclusion: Synthetic flavonoid derivatives hold great potential in the therapy of lung cancer. Continued research on their mechanistic insights and optimization can help to derive new anticancer therapeutics that are less harmful.
Meshram et al. (Tue,) studied this question.