title: Benzoquinones and terphenyl compounds as phosphodiesterase-4B inhibitors from a fungus of the order Chaetothyriales (MSX 47445).
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro , P.O. Box 26170, Greensboro, North Carolina 27402, USA.
authors.forename: Tamam
authors.initials: T
authors.lastname: El-Elimat
authors.forename: Mario
authors.initials: M
authors.lastname: Figueroa
authors.forename: Huzefa A
authors.initials: HA
authors.lastname: Raja
authors.forename: Tyler N
authors.initials: TN
authors.lastname: Graf
authors.forename: Audrey F
authors.initials: AF
authors.lastname: Adcock
authors.forename: David J
authors.initials: DJ
authors.lastname: Kroll
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Day
authors.forename: Mansukh C
authors.initials: MC
authors.lastname: Wani
authors.forename: Cedric J
authors.initials: CJ
authors.lastname: Pearce
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Oberlies
mesh_terms: D001203:Ascomycota / Q000737:chemistry* / Q000145:classification; D016227:Benzoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D018360:Crystallography, X-Ray; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000187:drug effects* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D058988:Phosphodiesterase 4 Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013730:Terphenyl Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D016227:Benzoquinones; D058988:Phosphodiesterase 4 Inhibitors; D013730:Terphenyl Compounds; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4