New Cytotoxic Naphthohydroquinone Dimers from <i>Rubia alata</i>

Abstract

Two novel naphthohydroquinone dimers with unprecedented skeletons, rubialatins A (<b>1</b>) and B (<b>2</b>), were isolated from the herbal plant <i>Rubia alata</i> together with their precursor, mollugin (<b>3</b>). The structures were elucidated on the basis of NMR spectra and crystal X-ray diffraction. Compound <b>1</b>, a racemate, was separated by chiral column chromatography, and the absolute configurations of the enantiomers were determined by the computational methods. Cytotoxicity of <b>1</b>–<b>3</b> was evaluated as well as the effect on the NF-κB pathway. Compound (+)-<b>1</b> showed cytotoxicity and could inhibit NF-κB pathway. Meanwhile, <b>2</b> showed cytotoxicity and a synergistic effect with TNF-α on NF-κB activation