Synthesis Of Hydroxycinnamic Acid Derivatives As Mitochondria-Targeted Antioxidants And Cytotoxic Agents

In order to develop agents with the superior chemopreventive and chemotherapeutic properties against hepatocellular carcinomas,mitochondria-targeted hydroxycinnamic acids（MitoHCAs）were synthesized via conjugation of hydroxycinnamic acids with a triphenylphosphonium cation.These synthetic compounds were evaluated for their antioxidant activities in hepatic mitochondria—including against OH·and ROO·-induced lipid peroxidation.H₂O₂production was decreased by significantly increasing glutathione peroxidase and catalase activities.In addition,cell proliferation data from three cell lines（HepG2,L02 and WI38）indicated that the MitoHCAs were selective for cancerous cells.Interestingly,the MitoHCAs both with or without Ca²⁺triggered mitochondrial dysfunction.In particular,an inhibitor of the mitochondrial permeability transition pore（mPTP）,CsA,attenuated mitochondrial damage and cell apoptosis,indicating that mPTP may be involved in the antiproliferative activity of MitoHCAs.