Shugeng Cao†, Douglas W. McMillin‡, Giselle Tamayo§, Jake Delmore‡, Constantine S. Mitsiades*‡, and Jon Clardy*†
† Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, United States
‡ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States
§ Unidad Estrategica de Bioprospeccion, Instituto Nacional de Biodiversidad (INBio), Santo Domingo de Heredia, Costa Rica
J. Nat. Prod., Article ASAP
DOI: 10.1021/np2009863
Publication Date (Web): March 29, 2012
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).
