Design, synthesis and anti-cancer evaluation of genistein-1,3,5-triazine derivatives

Twelve genistein-1,3,5-triazine derivatives were synthesized by nucleophilic substitution and characterized by 1H NMR, 13C NMR, IR, HR-MS and single crystal X-ray diffraction. The purity of target compounds was determined to be above 99% by HPLC. Antiproliferative activities of these compounds against MDA-MB-231 (breast), HeLa (cervical), HCT-116 (prostate) and Huh-7 (liver) cancer cell lines were evaluated by the MTT assay. Most genistein-1,3,5-triazine derivatives showed better anti-cancer activity than nuclear parent genistein. Compound 4i displayed the strongest antiproliferative activity against MDA-MB-231 cells (IC50 = 23.13 μM), which was better than 5-fluorouracil (IC50 = 78.04 μM). Further studies showed that compound 4i not only could inhibit the migration, invasion and adhesion of MDA-MB-231 cells, but also had great inhibitory effects on the proliferation of MDA-MB-231 tumor xenografts in vivo. In addition, ADME properties and toxicity prediction showed that these compounds may possess the properties to be drug candidates. Thus, compound 4i may be a promising lead compound for the treatment of breast cancer.