Synthesis and Biological Evaluation of Novel Genistein Amino Acid Ester Derivatives as Potential Anti-Tumor Agents

Thirty-one novel genistein amino acid ester derivatives were synthesized and evaluated for their anti-proliferative activities against HUVEC cells and five cancer cells lines (HCT-116, HeLa, HepG-2, MCF-7, MGC-803). Most of the amino acid ester derivatives exhibited more inhibitory activity than their parent compound genistein. In particular, compound 8 j (methyl(4-((5-hydroxy-3-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)butanoyl)tryptophanate) bearing tryptophan chain showed the most cytotoxicity against HCT-116 cells with IC50 value of 2.76 mu M. Further mechanistic studies indicated that compound 8 j suppressed HCT-116 cell metastasis and induced cell apoptosis in a dose-dependent manner. Cell cycle assay showed that compound 8 j arrested the HCT-116 cells to G1 phase. These studies suggested compound 8 j might be a potential candidate for developing new anticancer drugs.