Isolation, Structural Analyses and Biological Activity Assays against Chronic Lymphocytic Leukemia of Two Novel Cytochalasins — Sclerotionigrin A and B
Lene M. Petersen,
Tanja T. Bladt,
Claudia Dürr,
Martina Seiffert,
Jens C. Frisvad,
Charlotte H. Gotfredsen,
Thomas O. Larsen
Affiliations
Lene M. Petersen
Department of Systems Biology, Technical University of Denmark, Søltofts Plads B221, DK-2800 Kgs. Lyngby, Denmark
Tanja T. Bladt
Department of Systems Biology, Technical University of Denmark, Søltofts Plads B221, DK-2800 Kgs. Lyngby, Denmark
Claudia Dürr
German Cancer Research Center, Molecular Genetics, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
Martina Seiffert
German Cancer Research Center, Molecular Genetics, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
Jens C. Frisvad
Department of Systems Biology, Technical University of Denmark, Søltofts Plads B221, DK-2800 Kgs. Lyngby, Denmark
Charlotte H. Gotfredsen
Department of Chemistry, Technical University of Denmark, Kemitorvet, B201, DK-2800 Kgs. Lyngby, Denmark
Thomas O. Larsen
Department of Systems Biology, Technical University of Denmark, Søltofts Plads B221, DK-2800 Kgs. Lyngby, Denmark
Two new cytochalasins, sclerotionigrin A (1) and B (2) were isolated together with the known proxiphomin (3) from the filamentous fungus Aspergillus sclerotioniger. The structures and relative stereochemistry of 1 and 2 were determined based on comparison with 3, and from extensive 1D and 2D NMR spectroscopic analysis, supported by high resolution mass spectrometry (HRMS). Compounds 2 and 3 displayed cytotoxic activity towards chronic lymphocytic leukemia cells in vitro, with 3 being the most active.
