Synthesis and cancer cell growth inhibition effects of acetogenin analogs bearing ethylene glycol units for enhancing the water solubility

Abstract The syntheses of three thiophene-3-carboxamide analogs of annonaceous acetogenins were accomplished, where the obtained analogs bear ethylene glycol units that enhance their water solubilities. Evaluation of their growth inhibitory activities across 39 human cancer cell lines revealed that the analog bearing one ethylene glycol unit in the vicinity of its tetrahydrofuran ring moiety exhibited a comparable potent growth inhibitory activity to the lead compound, and the growth inhibitory patterns of these analogs are similar to those of mitochondrial complex I inhibitors. This result indicates the possibility of discovering new water-soluble antitumor agents derived from acetogenins through the introduction of ethylene glycol units.