Synthesis and cytotoxicity evaluation of 3-amino-2-hydroxypropoxyisoflavone derivatives

Soy isoflavones exert a wide variety of biological activities, such as antioxidant, anti-inflammatory and anti-cancer properties. Nuclear factor erythroid 2-related factor 2 (Nrf2), a bZip transcription factor, plays a key role in soy isoflavones induced protection against oxidative stress and cancer. To obtain more effective isofavones, a series of 7,4'-bis-(3-amino-2-hydroxypropoxy), 7 or 4'-(3-amino-2-hydroxypropoxy) isoflavone derivatives have been synthesized as potential antitumor agents and Nrf2/ARE (antioxidant response element) activators. The cytotoxicity of these compounds in human cancer cell lines MDA-MB-231, HT-29, HCT116, HepG2 and 7402 was tested by MTT assay. In this study, the cytotoxicity of compound 3b exhibited highest cytotoxic activity and at the safety dose range, it also strongly up-regulated antioxidant response element (ARE)-luciferase reporter activity. In addition, compound 3b induced Nrf2 nuclear translocation and upregulated its downstream target genes NQO-1 and HO-1 at protein level. Taken together, our results suggest that compound 3b could be a potential agent for cancer themotherapy or cancer chemoprevention.