Discovery of Ircinianin Lactones B and C—Two New Cyclic Sesterterpenes from the Marine Sponge <i>Ircinia wistarii</i>
Thomas Majer,
Keshab Bhattarai,
Jan Straetener,
Justus Pohlmann,
Patrick Cahill,
Markus O. Zimmermann,
Marc P. Hübner,
Marcel Kaiser,
Johan Svenson,
Michael Schindler,
Heike Brötz-Oesterhelt,
Frank M. Boeckler,
Harald Gross
Affiliations
Thomas Majer
Department of Pharmaceutical Biology, Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
Keshab Bhattarai
Department of Pharmaceutical Biology, Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
Jan Straetener
Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany
Justus Pohlmann
Institute for Medical Virology and Epidemiology, Section Molecular Virology, University Hospital Tübingen, 72076 Tübingen, Germany
Patrick Cahill
Cawthron Institute, 98 Halifax Street East, Nelson 7010, New Zealand
Markus O. Zimmermann
Lab for Molecular Design and Pharmaceutical Biophysics, Department of Pharmacy and Biochemistry, Institute of Pharmaceutical Sciences, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
Marc P. Hübner
Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, Germany
Marcel Kaiser
Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123 Allschwil, Switzerland
Johan Svenson
Cawthron Institute, 98 Halifax Street East, Nelson 7010, New Zealand
Michael Schindler
Institute for Medical Virology and Epidemiology, Section Molecular Virology, University Hospital Tübingen, 72076 Tübingen, Germany
Heike Brötz-Oesterhelt
Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany
Frank M. Boeckler
Lab for Molecular Design and Pharmaceutical Biophysics, Department of Pharmacy and Biochemistry, Institute of Pharmaceutical Sciences, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
Harald Gross
Department of Pharmaceutical Biology, Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
Two new ircinianin-type sesterterpenoids, ircinianin lactone B and ircinianin lactone C (7 and 8), together with five known entities from the ircinianin compound family (1, 3–6) were isolated from the marine sponge Ircinia wistarii. Ircinianin lactones B and C (7 and 8) represent new ircinianin terpenoids with a modified oxidation pattern. Despite their labile nature, the structures could be established using a combination of spectroscopic data, including HRESIMS and 1D/2D NMR techniques, as well as computational chemistry and quantum-mechanical calculations. In a broad screening approach for biological activity, the class-defining compound ircinianin (1) showed moderate antiprotozoal activity against Plasmodium falciparum (IC50 25.4 μM) and Leishmania donovani (IC50 16.6 μM).
