Butyrolactone I derivatives from Aspergillus terreus carrying an unusual sulfate moiety.
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).
Niu
Xuemei
X
Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Beutenbergstrasse 11a, D-07745 Jena, Germany.
Dahse
Hans-Martin
HM
Menzel
Klaus-Dieter
KD
Lozach
Olivier
O
Walther
Grit
G
Meijer
Laurent
L
Grabley
Susanne
S
Sattler
Isabel
I
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
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