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 1 (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-3 alpha/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 1 (3). Likewise, butyrolactone I 3-sulfate (1) exhibited moderate cytotoxicity solely against HeLa cells (CC50 = 80.7 mu M).