title: Bioactive metabolites from Chaetomium aureum: structure elucidation and inhibition of the Hsp90 machine chaperoning activity.
abstract: Chemical investigation of the EtOAc extract of the fungus Chaetomium aureum, an endophyte of the Moroccan medicinal plant Thymelaea lythroides, afforded one new resorcinol derivative named chaetorcinol, together with five known metabolites. The structures of the isolated compounds were determined on the basis of one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry as well as by comparison with the literature. All compounds were tested for their activity towards the Hsp90 chaperoning machine in vitro using the progesterone receptor (PR) and rabbit reticulocyte lysate (RRL). Among the isolated compounds, only sclerotiorin efficiently inhibited the Hsp90 machine chaperoning activity. However, sclerotiorin showed no cytotoxic effect on breast cancer Hs578T, MDA-MB-231 and prostate cancer LNCaP cell lines. Interestingly, deacetylation of sclerotiorin increased its cytotoxicity toward the tested cell lines over a period of 48 h.
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Building 26.23, 40225 Düsseldorf, Germany; Laboratory of Pharmacology and Toxicology, University Mohammed V Souissi, Rabat, Morocco; Department of Organic Chemistry, University of Wuppertal, Gaußstr. 20, 42097 Wuppertal, Germany.
authors.forename: Fatima Zahra
authors.initials: FZ
authors.lastname: Kabbaj
authors.affiliation: Cancer Research Center, Molecular Chaperones Biology, Georgia Regents University, 1410 Laney Walker Blvd, CN-3151, Augusta, GA 30912, United States.
authors.forename: Su
authors.initials: S
authors.lastname: Lu
authors.affiliation: Laboratory of Pharmacology and Toxicology, University Mohammed V Souissi, Rabat, Morocco.
authors.forename: My El Abbés
authors.initials: Mel A
authors.lastname: Faouzi
authors.affiliation: Laboratory of Pharmacology and Toxicology, University Mohammed V Souissi, Rabat, Morocco.
authors.forename: Bouchra
authors.initials: B
authors.lastname: Meddah
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Building 26.23, 40225 Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
authors.affiliation: Laboratory of Pharmacology and Toxicology, University Mohammed V Souissi, Rabat, Morocco.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Cherrah
authors.affiliation: Department of Organic Chemistry, University of Wuppertal, Gaußstr. 20, 42097 Wuppertal, Germany.
authors.forename: Hans-Josef
authors.initials: HJ
authors.lastname: Altenbach
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Building 26.23, 40225 Düsseldorf, Germany.
authors.forename: Amal H
authors.initials: AH
authors.lastname: Aly
authors.affiliation: Cancer Research Center, Molecular Chaperones Biology, Georgia Regents University, 1410 Laney Walker Blvd, CN-3151, Augusta, GA 30912, United States. Electronic address: achadli@gru.edu.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Chadli
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Building 26.23, 40225 Düsseldorf, Germany. Electronic address: abdessamad.debbab@uni-duesseldorf.de.
authors.forename: Abdessamad
authors.initials: A
authors.lastname: Debbab
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002597:Chaetomium / Q000737:chemistry*; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011817:Rabbits; D012118:Resorcinols / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D012118:Resorcinols
keywords: Bioactive metabolites; Chaetomium aureum; Cytotoxicity; Hsp90; Structure elucidation