Synthesis and biological evaluation of novel 2-alkoxycarbonylallylester phosphonium derivatives as potential anticancer agents

Abstract

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 µM concentrations. Further studies reveal that β-substituted BH bromide derived phosphonium derivatives enhance the biological activity to low µM IC₅₀ values. In vitrometabolic 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.

Keywords: Anticancer agent; Baylis-Hillman reaction; MTT and SRB assay; MitoStress test; Phosphonium derivatives.