Synthesis, Evaluation and Comparative analysis of Apigenin and Eupatilin Analogue for Anti-Carcinogenic Properties

AbstractThis study evaluates the anticancer potential of synthetic apigenin derivatives and the naturalflavonoid eupatilin. The apigenin derivatives, particularly the 4a-4j series, exhibited superiorantiproliferative activity against various human cancer cell lines, including breast, lung,cervical, and colon cancer cells. Compound 4j emerged as the most potent analogue, displayingan IC50 value of 2.8 μM against MCF-7 cells, significantly stronger than the parent apigenin.Mechanistic studies revealed that 4j promotes apoptosis, increases intracellular ROSgeneration, and induces G2/M cell cycle arrest, confirming its multitargeted mechanism ofaction. In comparison, eupatilin demonstrated comparable potency and a broaderpharmacological profile, including anti-inflammatory and gastroprotective effects. Thesefindings highlight the potential of both synthetic and natural flavonoids as promising leads forthe development of novel anticancer therapeutics, offering opportunities for further structuraloptimization and therapeutic exploration.