Discovery of Ircinianin Lactones B and C-Two New Cyclic Sesterterpenes from the Marine Sponge Ircinia wistarii

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

doi:10.3390/md20080532

Discovery of Ircinianin Lactones B and C-Two New Cyclic Sesterterpenes from the Marine Sponge Ircinia wistarii

Mar Drugs. 2022 Aug 19;20(8):532. doi: 10.3390/md20080532.

Authors

Thomas Majer¹, Keshab Bhattarai¹, Jan Straetener², Justus Pohlmann³, Patrick Cahill⁴, Markus O Zimmermann⁵, Marc P Hübner^{6

7}, Marcel Kaiser^{8

9}, Johan Svenson⁴, Michael Schindler³, Heike Brötz-Oesterhelt^{2

10

11}, Frank M Boeckler^{5

12}, Harald Gross^{1

10

11}

Affiliations

¹ Department of Pharmaceutical Biology, Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
² Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
³ Institute for Medical Virology and Epidemiology, Section Molecular Virology, University Hospital Tübingen, 72076 Tübingen, Germany.
⁴ Cawthron Institute, 98 Halifax Street East, Nelson 7010, New Zealand.
⁵ 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.
⁶ Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, Germany.
⁷ German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.
⁸ Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123 Allschwil, Switzerland.
⁹ Faculty of Science, University of Basel, Petersplatz 1, 4002 Basel, Switzerland.
¹⁰ Cluster of Excellence 'Controlling Microbes to Fight Infections', University of Tübingen, 72076 Tübingen, Germany.
¹¹ German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany.
¹² Interfaculty Institute for Biomedical Informatics (IBMI), University of Tübingen, Sand 14, 72076 Tübingen, Germany.

Abstract

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).

Keywords: Ircinia wistarii; Leishmania donovani; NCI-60; Plasmodium falciparum; antiprotozoal activity; bioactivity screening; ircinianin-derivates; sesterterpene; sponge.

MeSH terms

Animals
Lactones / chemistry
Lactones / pharmacology
Molecular Structure
Porifera* / chemistry
Sesterterpenes* / chemistry
Sesterterpenes* / pharmacology
Terpenes / pharmacology

Substances

Lactones
Sesterterpenes
Terpenes
ircinianin

Grants and funding

390838134/Cluster of Excellence ´Controlling microbes to fight infection´