Jordan University of Science and Technology

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


Authors:  Tamam El-Elimat, Mario Figueroa, Huzefa A. Raja, Tyler N. Graf, Audrey F. Adcock, David J. Kroll, Cynthia S. Day, Mansukh C. Wani, Cedric J. Pearce, and Nicholas H. Oberlies

Abstract:  
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-II0204-207: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.