title: Bioactive Constituents from an Endophytic Fungus, Penicillium polonicum NFW9, Associated with Taxus fauna.
abstract: BACKGROUND
  Endophytic fungi are being recognized as vital and untapped sources of a variety of structurally novel and unique bioactive secondary metabolites in the field of natural products drug discovery. Herein, this study reports the isolation and characterization of secondary metabolites from an endophytic fungus Penicillium polonicum (NFW9) associated with Taxus fuana.
  
  
  METHODS
  The extracts of the endophytic fungus cultured on potato dextrose agar were purified using several chromatographic techniques. Biological evaluation was performed based on their abilities to inhibit tumor necrosis factor-alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB) and cytotoxicity assays.
  
  
  RESULTS
  Bioactivity-directed fractionation of the ethyl acetate extract of a fermentation culture of an endophytic fungus, Penicillium polonicum led to the isolation of a dimeric anthraquinone, (R)- 1,1',3,3',5,5'-hexahydroxy-7,7'-dimethyl[2,2'-bianthracene]-9,9',10,10'-tetraone (1), a steroidal furanoid (-)-wortmannolone (2), along with three other compounds (3-4). Moreover, this is the first report on the isolation of compound 1 from an endophytic fungus. All purified metabolites were characterized by NMR and MS data analyses. The stereo structure of compound 1 was determined by the measurement of specific optical rotation and CD spectrum. The relative stereochemistry of 2 was confirmed by single-crystal X-ray diffraction. Compounds 2-3 showed inhibitory activities in the TNF-α-induced NF-κB assay with IC50 values in the range of 0.47-2.11 µM. Compounds 1, 4 and 5 showed moderate inhibition against NF-κB and cancer cell lines.
  
  
  CONCLUSIONS
  The endophytic fungus Penicillium polonicum of Taxus fuana is capable of producing biologically active natural compounds. Our results provide a scientific rationale for further chemical investigations into endophyte-producing natural products, drug discovery and development.
authors.affiliation: Department of Pharmacy, COMSATS Institute of Information Technology (CIIT), Abbottabad. Pakistan.
authors.forename: Nighat
authors.initials: N
authors.lastname: Fatima
authors.affiliation: School of Cosmetic Science, Mae Fah Luang University, Tasud, Muang, Chiang Rai 57100. Thailand.
authors.forename: Tawanun
authors.initials: T
authors.lastname: Sripisut
authors.affiliation: Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI, 96720. United States.
authors.forename: Ui J
authors.initials: UJ
authors.lastname: Youn
authors.affiliation: Department of Microbiology, Quaid-i-Azam University, Islamabad, 45320. Pakistan.
authors.forename: Safia
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Department of Pharmacy, Quaid-i-Azam University, Islamabad, 45320. Pakistan.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Ul-Haq
authors.affiliation: Division of Pharmacy Practice and Administration and Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, 43210. United States.
authors.forename: Ulyana
authors.initials: U
authors.lastname: Munoz-Acuna
authors.affiliation: Chemistry Department, University of Hawai'i at Hilo, Hilo, HI, 96720. United States.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Simmons
authors.affiliation: Department of Microbiology, Quaid-i-Azam University, Islamabad, 45320. Pakistan.
authors.forename: Muneer A
authors.initials: MA
authors.lastname: Qazi
authors.affiliation: Department of Microbiology, Quaid-i-Azam University, Islamabad, 45320. Pakistan.
authors.forename: Muniba
authors.initials: M
authors.lastname: Jadoon
authors.affiliation: Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI, 96720. United States.
authors.forename: Ghee T
authors.initials: GT
authors.lastname: Tan
authors.affiliation: Division of Pharmacy Practice and Administration and Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, 43210. United States.
authors.forename: Esperanza J C
authors.initials: EJC
authors.lastname: de Blanco
authors.affiliation: Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI, 96720. United States.
authors.forename: Leng C
authors.initials: LC
authors.lastname: Chang
mesh_terms: D000730:Androstadienes / Q000302:isolation & purification / Q000494:pharmacology*; D000880:Anthraquinones / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D010407:Penicillium / Q000737:chemistry*; D013237:Stereoisomerism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000077191:Wortmannin
chemical_list: C000625187:1,1',3,3',5,5'-hexahydroxy-7,7'-dimethyl(2,2'-bianthracene)-9,9',10,10'-tetraone; D000730:Androstadienes; D000880:Anthraquinones; D000970:Antineoplastic Agents; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C000625188:wortmannolone; D017239:Paclitaxel; D000077191:Wortmannin
keywords: Penicillium sp; Taxus fuana; cytotoxicity; endophytic fungi; furanosteroids; natural products