Total Synthesis of Thelephantin O, Vialinin A/Terrestrin A, and Terrestrins B–D

The first total synthesis of natural, unsymmetrical 2′,3′-diacyloxy-<i>p</i>-terphenyls, thelephantin O (<b>1</b>) and terrestrins C and D (<b>2</b> and <b>3</b>, respectively), was achieved via a practical route which was also applicable to the synthesis of the symmetrical diesters vialinin A/terrestrin A (<b>4</b>) and terrestrin B (<b>5</b>). Compounds <b>1</b>–<b>5</b> exhibited cytotoxicity against cancer cells (HepG2 and Caco2) with IC₅₀ values of 13.6–26.7 μmol/L

<i>p</i>‑Terphenyl Derivatives from the Mushroom Thelephora aurantiotincta Suppress the Proliferation of Human Hepatocellular Carcinoma Cells via Iron Chelation

A novel 2′,3′-dihydroxy-<i>p</i>-terphenyl derivative, thelephantin O (TO), which has cancer-selective cytotoxicity, was isolated. This study investigated the underlying basis of the cytotoxicity of 2′,3′-dihydroxy-<i>p-</i>terphenyl compounds in view of their ability to chelate metal ions. FeCl₂ significantly reduced TO-induced cytotoxicity, whereas several other salts of transition metals and alkaline-earth metals did not. A structure–activity relationship study using newly synthesized <i>p</i>-terphenyl derivatives revealed that <i>o</i>-dihydroxy substitution of the central benzene ring was necessary for both the cytotoxicity and Fe²⁺ chelation of the compounds. Real-time PCR array and cell cycle analysis revealed that the TO-induced cytotoxicity was attributed to cell cycle arrest at the G1 phase via well-known cell cycle-mediated genes. The TO-induced changes in the cell cycle and gene expression were completely reversed by the addition of FeCl₂. Thus, it was concluded that Fe²⁺ chelation occurs upstream in the pivotal pathway of 2′,3′-dihydroxy-<i>p</i>-terphenyl-induced inhibition of cancer cell proliferation