Benzoquinones and Terphenyl Compounds As Phosphodiesterase-4B Inhibitors from a Fungus of the Order Chaetothyriales (MSX 47445)

El-Elimat, T., Figueroa, M., Raja, H. A., Graf, T. N., Adcock, A. F., Kroll, D. J., ... Oberlies, N. H. (2013). Benzoquinones and Terphenyl Compounds As Phosphodiesterase-4B Inhibitors from a Fungus of the Order Chaetothyriales (MSX 47445). Journal of Natural Products, 76(3), 382-387. DOI: 10.1021/np300749w

Three bioactive compounds were isolated from an organic extract of an ascomycete fungus of the order Chaetothyriales (MSX 47445) using bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Of these, two were benzoquinones [betulinan A (1) and betulinan C (3)), and the third was a terphenyl compound, BTH-I10204-207:A (2). The structures were elucidated using a set of spectroscopic and spectrometric techniques; the structure of the new compound (3) was confirmed via single-crystal X-ray diffraction. Compounds 1-3 were evaluated for cytotoxicity against a human cancer cell panel, for antimicrobial activity against Staphylococcus aureus and Candida albicans, and for phosphodiesterase (PDE4B2) inhibitory activities. The putative binding mode of 1-3 with PDE4B2 was examined using a validated docking protocol, and the binding and enzyme inhibitory activities were correlated