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      • Pro-Apoptotic and Immunostimulatory Tetrahydroxanthone Dimers from the Endophytic Fungus Phomopsis longicolla

        Rö,nsberg, David,Debbab, Abdessamad,Má,ndi, Attila,Vasylyeva, Vera,Bö,hler, Philip,Stork, Bjö,rn,Engelke, Laura,Hamacher, Alexandra,Sawadogo, Richard,Diederich, Marc,Wray, Vict American Chemical Society 2013 Journal of organic chemistry Vol.78 No.24

        <P>Four tetrahydroxanthone dimers (<B>1</B>–<B>4</B>) and four biogenetically related monomers (<B>5</B>–<B>8</B>), including the new derivatives <B>4</B>–<B>6</B>, were isolated from the endophyte Phomopsis longicolla. The absolute configurations of <B>2</B>–<B>4</B> were established for the first time by TDDFT electronic circular dichroism calculations, and that of phomoxanthone A (<B>1</B>) was revised by X-ray crystallography. Phomoxanthone A (<B>1</B>) showed the strongest pro-apoptotic activity when tested against a panel of human cancer cell lines, including cisplatin-resistant cells, whereas it was up to 100-fold less active against healthy blood cells. It was also the most potent activator of murine T lymphocytes, NK cells, and macrophages, suggesting an activation of the immune system in parallel to its pro-apoptotic activity. This dual effect in combating cancer cells could help in fighting resistance during chemotherapy. Preliminary structure–activity studies of isolated compounds and derivatives obtained by semisynthesis (<B>9a</B>–<B>11</B>) hinted at the location of the biaryl axis and the presence of acetyl groups as important structural elements for the biological activity of the studied tetrahydroxanthones.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/joceah/2013/joceah.2013.78.issue-24/jo402066b/production/images/medium/jo-2013-02066b_0011.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jo402066b'>ACS Electronic Supporting Info</A></P>

      • Protein Kinase and HDAC Inhibitors from the Endophytic Fungus <i>Epicoccum nigrum</i>

        El Amrani, Mustapha,Lai, Daowan,Debbab, Abdessamad,Aly, Amal H.,Siems, Karsten,Seidel, Carole,Schnekenburger, Michael,Gaigneaux, Anthoula,Diederich, Marc,Feger, Daniel,Lin, Wenhan,Proksch, Peter American Chemical Society and American Society of 2014 Journal of natural products Vol.77 No.1

        <P>A chemical investigation of the endophytic fungus <I>Epicoccum nigrum</I> isolated from leaves of <I>Mentha suaveolens</I> collected in Morocco resulted in the isolation of five new polyketides, epicocconigrones A and B (<B>1</B> and <B>2</B>), 3-methoxyepicoccone B (<B>3</B>), 3-methoxyepicoccone (<B>4</B>), and 2,3,4-trihydroxy-6-(methoxymethyl)-5-methylbenzaldehyde (<B>5</B>), together with five known compounds (<B>6</B>–<B>10</B>). The structures of the new compounds were unambiguously determined by extensive analysis of the 1D and 2D NMR and mass spectroscopic data. Compounds <B>1</B> and <B>10</B> showed potent inhibition of at least 15 protein kinases with IC<SUB>50</SUB> values ranging from 0.07 to 9.00 μM. Moreover, compounds <B>1</B> and <B>10</B> inhibited histone deacetylase (HDAC) activities with IC<SUB>50</SUB> values of 9.8 and 14.2 μM, respectively. A preliminary structure–activity relationship is discussed. Interestingly, compounds <B>1</B> and <B>10</B> exert mainly cytostatic effects in human lymphoma RAJI and U-937 cell lines.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jnprdf/2014/jnprdf.2014.77.issue-1/np4005745/production/images/medium/np-2013-005745_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/np4005745'>ACS Electronic Supporting Info</A></P>

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