Synthesis And Biological Evaluation Of Novel 2-Alkoxycarbonylallylester Phosphonium Derivatives As Potential Anticancer Agents

Several phosphonium derivatives have been synthesized from Baylis-Hillman (BH) reaction derived allyl bromides and aryl phosphines as mitochondria targeting anticancer agents. In vitro cell proliferation inhibition studies on various solid tumor cell lines indicate that most of the compounds exhibit IC50 values in mu M concentrations. Further studies reveal that beta-substituted BH bromide derived phosphonium derivatives enhance the biological activity to low mu M IC50 values. In vitro metabolic studies show that the lead candidate compound 16 inhibits the production of mitochondrial ATP, increases the proton leak within the mitochondrial membrane and abolishes the spare respiratory capacity in a concentration dependent manner.