title: Butyrolactone I derivatives from Aspergillus terreus carrying an unusual sulfate moiety.
abstract: In our ongoing search for new bioactive metabolites from microbial resources, Aspergillus terreus (HKI0499) was examined by chemical metabolite profiling. Together with the known butyrolactone I ( 3), the unusual sulfate derivatives butyrolactone I 3-sulfate ( 1) and butyrolactone I 4''-sulfate ( 2) were discovered. The chemical structures were determined by NMR and MS data analyses. All compounds were tested on CDK1/cyclin B, CDK5/p25, DYRK1A, CK1, and GSK-3alpha/beta kinases; compounds 2 and 3 were also evaluated for their cytotoxic and antiproliferative activities. Butyrolactone I 3-sulfate ( 1) exhibited specific inhibitory activity against CDK1/cyclin B and CDK5/p25, yet 15-30-fold less than butyrolactone I ( 3). Likewise, butyrolactone I 3-sulfate ( 1) exhibited moderate cytotoxicity solely against HeLa cells (CC 50 = 80.7 microM).
authors.affiliation: Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Beutenbergstrasse 11a, D-07745 Jena, Germany.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Niu
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Dahse
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Menzel
authors.forename: Olivier
authors.initials: O
authors.lastname: Lozach
authors.forename: Grit
authors.initials: G
authors.lastname: Walther
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: Susanne
authors.initials: S
authors.lastname: Grabley
authors.forename: Isabel
authors.initials: I
authors.lastname: Sattler
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001230:Aspergillus / Q000737:chemistry*; D001921:Brain / Q000201:enzymology; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors; D004354:Drug Screening Assays, Antitumor; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D006801:Humans; D009865:Oocytes / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013215:Starfish / Q000201:enzymology; D013431:Sulfates / Q000737:chemistry*; D013552:Swine; D000097603:Dyrk Kinases
chemical_list: D015107:4-Butyrolactone; D000970:Antineoplastic Agents; D016203:CDC2 Protein Kinase; D051360:Cyclin-Dependent Kinase 5; D038362:Glycogen Synthase Kinase 3; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D013431:Sulfates; D000097603:Dyrk Kinases; C082868:butyrolactone I