Cytotoxic Activity of Dietary Lignan and Its Derivatives: Structure–Cytotoxic Activity Relationship of Dihydroguaiaretic Acid

Cytotoxic activities of synthesized lignan derivatives were estimated by WST-8 reduction assay against HL-60 and HeLa cells to show the structure–activity relationship. The activities of some effective compounds were examined against Colon 26 and Vero cells. Dietary secoisolariciresinol (SECO, 1) and its metabolite, 9,9′-anhydro­secoiso­lariciresinol (2), did not show the cytotoxic activity. On the other hand, all stereoisomers of dihydroguaiaretic acid (DGA, 9,9′-dehydroxy­secoiso­lariciresinol, 3–5) exhibited the activity (IC₅₀: around 30 μM). The IC₅₀ value of (8R,8′R)-9-butyl DGA derivative 13 was around 6 μM. This fact means that the hydrophobic group was advantageous for higher activity at 9- and 9′-positions. By the evaluation of the effect of 7and 7′-aryl group on the activity, we discovered the highest activity of (8R,8′R)-7-(3-hydroxy-4-methoxyphenyl)-7′-(2-ethoxyphenyl) DGA derivative 47 showing around 1 μM of IC₅₀ value, which is about 24-fold higher activity than that of natural (8R,8′R)-DGA. The derivative of dietary lignan showed the high cytotoxic activity.