Caged xanthones displaying protein tyrosine phosphatase 1B (PTP1B) inhibition from <i>Cratoxylum cochinchinense</i>

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>Four new caged xanthones (<B>1</B>–<B>4</B>) and two known compounds (<B>5</B>, <B>6</B>) were isolated from the roots of <I>Cratoxylum cochinchinense</I>, a polyphenol rich plant, collected in China. The structures of the isolated compounds (<B>1</B>–<B>6</B>) were characterized by obtaining their detailed spectroscopic data. In particular, compounds <B>1</B> and <B>6</B> were fully identified by X-ray crystallographic data. The isolated compounds (<B>1</B>–<B>6</B>) were evaluated against protein tyrosine phosphatase 1B (PTP1B), which plays an important role in diabetes, obesity, and cancer. Among these compounds, <B>3</B>, <B>4</B>, and <B>6</B> displayed significant inhibition with IC<SUB>50</SUB> values of 76.3, 43.2, and 6.6 µM, respectively. A detailed kinetic study was conducted by determining <I>K</I> <SUB>m</SUB>, <I>V</I> <SUB>max</SUB>, and the ratio of <I>K</I> <SUB>ik</SUB> and <I>K</I> <SUB>iv</SUB>, which revealed that all the compounds behaved as competitive inhibitors.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Six caged xanthones including four new ones were isolated from the roots of <I>Cratoxylum cochinchinense.</I> </LI> <LI> Structural elucidations of all compounds were performed with detailed spectroscopic data including 2D NMR and HREIMS analyses. </LI> <LI> PTP1B inhibitory activities were investigated, among them compound <B>6</B> displayed the most potent inhibition (IC<SUB>50</SUB> = 6.6 μM). </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>