| Summary: | Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B (<b>1</b>), β-resoantarctines A-C (<b>3</b>, <b>5</b>, <b>6</b>) and 8-dehydro-β-resoantarctine A (<b>4</b>), together with known 14-hydroxyasperentin (5′-hydroxyasperentin) (<b>2</b>), were isolated from the ethyl acetate extract of the fungus <i>Penicillium antarcticum</i> KMM 4685 associated with the brown alga <i>Sargassum miyabei</i>. The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher’s method, and the biogenetic pathways for compounds <b>3</b>–<b>6</b> were proposed. For the very first time, the relative configuration of the C-14 center of a known compound <b>2</b> was assigned via analyses of magnitudes of the vicinal coupling constants. The new metabolites <b>3</b>–<b>6</b> were biogenically related to resorcylic acid lactones (RALs); however, they did not possess lactonized macrolide elements in their structures. Compounds <b>3</b>, <b>4</b> and <b>5</b> exhibited moderate cytotoxic activity in LNCaP, DU145 and 22Rv1 human prostate cancer cells. Moreover, these metabolites could inhibit the activity of p-glycoprotein at their noncytotoxic concentrations and consequently synergize with docetaxel in p-glycoprotein-overexpressing drug-resistant cancer cells.
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