Phosphoramidate protides of five flavones and their antiproliferative activity against HepG2 and L-O2 cell lines

A series of flavone-7-phosphoramidate derivatives were synthesized and tested for their antiproliferative activity in vitro against human hepatoma cell line HepG2 and human normal hepatic cell line L-O2. Compound 8d, 16d and 17d, incorporating the amino acid alanine, exhibited high inhibitory activity on HepG2 cell line with IC50 values of 9.0 μmol/L, 5.5 μmol/L and 6.6 μmol/L. The introduction of acyl groups played a pivotal role in the selective inhibition toward human hepatoma HepG2 cells, except for compound 8a, 9a and 16b. Compound 8d, 16d and 17d could significantly induce G2/M arrest in HepG2 cells. Specially, Compound 16d could lead early apoptosis in HepG2 cells. [Display omitted] •A series of flavone-7-phosphoramidate derivatives was synthesized.•Some derivatives had shown selective inhibition against hepatoma HepG2 cells.•Compounds 8d, 16d and 17d could almost thoroughly induce HepG2 cells in G2/M phase.•Phosphoramidate group significantly improved the apoptosis induction of compound 16d.•Compound 16d (IC50 = 5.5 ± 1.3 μM) induced early apoptosis in HepG2 cells.