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

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

Key HMBC, ¹H-¹H COSY, and ROESY correlations of 1.

<p>Key HMBC, ¹H-¹H COSY, and ROESY correlations of 1.</p

¹H NMR spectra comparison of rubipodanin A (1, top) and RA-V (4, bottom).

<p>¹H NMR spectra comparison of rubipodanin A (1, top) and RA-V (4, bottom).</p

Chemical structures of 1–7.

<p>Chemical structures of 1–7.</p