Synthesis and biological evaluation of nitric oxide-releasing sixalkoxyl biphenyl derivatives as anticancer agents

A series of novel nitric oxide-donating sixalkoxyl biphenyl derivatives (14a–l) were synthesized by coupling furoxan with alkoxyl biphenyl skeleton using amino acids as the spacers, and their cytotoxicity against HepG2 cells in vitro were evaluated by MTT method. It was found that 14c, 14d, 14f, 14i, 14j and 14k showed more potent cytotoxic activities than control 5-fluorouracil. NO release assay of target compounds indicated that the maximum amount of NO released by most active compounds 14c and 14j was about 6 × 10−2 μmol/L, whereas 14a and 14h with very weak activity only released NO of 1 × 10−2 μmol/L.