Inhibition of Tumor Cells Interacting with Stromal Cells by Xanthones Isolated from a Costa Rican Penicillium sp.




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Cao, Shugeng
McMillin, Douglas W.
Tamayo Castillo, Giselle
Delmore, Jake
Mitsiades, Constantine S.
Clardy, Jon

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CR1642D, an endophytic isolate of Penicillium sp. collected from a Costa Rican rainforest, was identified through a high-throughput approach to identify natural products with enhanced antitumor activity in the context of tumor–stromal interactions. Bioassay-guided separation led to the identification of five xanthones (1–5) from CR1642D. The structures of the xanthone dimer penexanthone A (1) and monomer penexanthone B (2) were elucidated on the basis of spectroscopic analyses, including 2D NMR experiments. All of the compounds were tested against a panel of tumor cell lines in the presence and absence of bone marrow stromal cells. Compound 3 was the most active, with IC50 values of 1–17 μM, and its activity was enhanced 2-fold against tumor cell line RPMI8226 in the presence of stromal cells (IC50 1.2 μM, but 2.4 μM without stromal cells).


Palabras clave

Alkyls, Aromatic compounds, Monomers, Xanthones, CELLS, COSTA RICA