Design and synthesis of a novel β-anhydroicartin derivative targeting tumor cell mitochondria based on the regulation of p16INK4a and its biological activity evaluation.

Based on the regulation of β-anhydroicaritin on the stability of p16INK4a encoded by CDKN2A gene, nine novel triphenylphosphine derivatives targeting tumor cell mitochondria were synthesized. Compound increased the ability to inhibit lung cancer A549 cells by 24 times compared with 5-fluorouracil. Biological studies have shown that compound significantly promotes early apoptosis and induces mitochondrial dysfunction in A549 cells. Further studies showed that compound arrested 73% of the cells in the G0/G1 phase, preventing the cells from entering the DNA synthesis phase. In summary, compound is expected to be developed as a new targeted anti-tumor drug.