Synthesis and anticancer properties of phenyl benzoate derivatives possessing a terminal hydroxyl group

Abstract

To assess the cytotoxic effects on A549 human lung cancer cells, we investigated a liquid-crystalline compound possessing a terminal hydroxyl group at concentrations of 0.1–20 μM. The compound, 4-butylphenyl 4-(6-hydroxyhexyloxy)benzoate (2), showed marked cell-growth inhibition at concentrations higher than 5 μM. Cell accumulation in the Sub-G1 phase indicating apoptosis was observed only at the highest concentration. Dynamic light scattering measurements show that the molecules form a spherical nanoparticle with a diameter of 130–170 nm at concentrations of 5–20 μM. We prepared the corresponding dimeric compounds and investigated their anticancer activity. The 1,2-benzene derivative, 1,2-bis[4-(6-hydroxyhexyloxy)benzoyloxy]benzene (4), exhibited cell-growth inhibition without affecting the cell cycle. However, the 1,3-benzene derivative, 1,3-bis[4-(6-hydroxyhexyloxy)benzoyloxy]benzene (5), was found to induce marked cell accumulation in the Sub-G1 phase. Furthermore, we assessed the cytotoxic effects of compounds 2, 4 and 5 on SW480 colon cancer cells and THP1 leukemic cells, as well as on WI-38 normal fibroblast cells. Both compounds 2 and 5 suppressed the growth of the solid cancer cells (A549 and SW480) more strongly compared with that of the hematological cancer cells (THP1). Unexpectedly, they also exhibited a strong cytotoxicity against the normal cells. We discuss the structure–property relationship in the anticancer activity of the mesogenic compounds.