Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 19;20(8):532.
doi: 10.3390/md20080532.

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

Thomas Majer  1 , Keshab Bhattarai  1 , Jan Straetener  2 , Justus Pohlmann  3 , Patrick Cahill  4 , Markus O Zimmermann  5 , Marc P Hübner  6   7 , Marcel Kaiser  8   9 , Johan Svenson  4 , Michael Schindler  3 , Heike Brötz-Oesterhelt  2   10   11 , Frank M Boeckler  5   12 , Harald Gross  1   10   11
Affiliations

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

Thomas Majer et al. Mar Drugs. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of the ircinianin-sesterterpene family. The center image depicts the Ircinia wistarii sample of this study.
Figure 2
Figure 2
Stacked 1H-NMR spectra of ircinianin (1) and ircinianin lactones A-C (6–8), recorded in d4-MeOH with the characteristic “signal-fingerprint” of the ircinianin-like scaffold in the 0.6 to 5.4 ppm region (red box with solid lines). The signals of the sidechain heterocycles appear between 5.5 to 7.5 ppm. Symbols denote the peak assignments in all 1H NMR spectra, which are visualized in the chemical structure on the right (red box with dashed lines). Key: blue symbols denote hydrogens of the tricyclic spirotetronic acid backbone; green symbols denote hydrogens of the alkyl side chain, R = terminal sidechain heterocycle. Hash symbol denotes residual methanol.
Figure 3
Figure 3
Key NMR correlations for 7.
Figure 4
Figure 4
Key NMR correlations for 8.
Figure 5
Figure 5
(A) Superimposition of the lowest energy conformer obtained for the 1S- (purple) and 1R-(brown) epimer of ircinianin lactone C (8). Dashed lines indicate the hydrogen bonds formed by OH-1 and OH-22. (B) 1R-epimer of 8. Dashed lines indicate distance measurements; green through space interactions are in agreement with observed NOE correlations, while the red contact was expected to be detectable, but was absent in the corresponding NOESY NMR spectrum. (C) 1S-epimer of 8. Green dashed lines indicate through space interactions, which agree with the observed NOE correlations.
Figure 6
Figure 6
Proposed biosynthetic pathway. Substructures in green boxes are associated with isolated molecules, as mentioned above. Red-framed structures indicate what are so far only hypothetical structure analogues following the predicted biosynthetic scheme.
See this image and copyright information in PMC

References

    1. Carroll A.R., Copp B.R., Davis R.A., Keyzers R.A., Prinsep M.R. Marine natural products. Nat. Prod. Rep. 2021;38:362–413. doi: 10.1039/D0NP00089B. - DOI - PubMed
    1. Manes L.V., Naylor S., Crews P., Bakus G.J. Suvanine, a novel sesterterpene from an Ircinia marine sponge. J. Org. Chem. 1985;50:284–286. doi: 10.1021/jo00202a030. - DOI
    1. Höller U., König G.M., Wright A.D. Two New Sesterterpene Tetronic Acids from the Marine Sponge Ircinia oros. J. Nat. Prod. 1997;60:832–835. doi: 10.1021/np970170y. - DOI
    1. Wright A.E., McCarthy P.J., Schulte G.K. Sulfircin: A new sesterterpene sulfate from a deep-water sponge of the genus Ircinia. J. Org. Chem. 1989;54:3472–3474. doi: 10.1021/jo00275a037. - DOI
    1. Barrow C.J., Blunt J.W., Munro M.H.G., Perry N.B. Oxygenated Furanosesterterpene Tetronic Acids from a Sponge of the Genus Ircinia. J. Nat. Prod. 1988;51:1294–1298. doi: 10.1021/np50060a047. - DOI

LinkOut - more resources