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

Abstract

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 13 increased the ability to inhibit lung cancer A549 cells by 24 times compared with 5-fluorouracil. Biological studies have shown that compound 13 significantly promotes early apoptosis and induces mitochondrial dysfunction in A549 cells. Further studies showed that compound 13 arrested 73% of the cells in the G0/G1 phase, preventing the cells from entering the DNA synthesis phase. In summary, compound 13 is expected to be developed as a new targeted anti-tumor drug.