Using UHPLC-MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

Sasha Hayes; Aya C Taki; Kah Yean Lum; Joseph J Byrne; Merrick G Ekins; Robin B Gasser; Rohan A Davis

doi:10.3762/bjoc.18.164

Using UHPLC-MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

Beilstein J Org Chem. 2022 Nov 15:18:1544-1552. doi: 10.3762/bjoc.18.164. eCollection 2022.

Authors

Sasha Hayes¹, Aya C Taki², Kah Yean Lum¹, Joseph J Byrne², Merrick G Ekins³, Robin B Gasser², Rohan A Davis¹

Affiliations

¹ Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Brisbane, 4111, Australia.
² Department of Veterinary Biosciences, The University of Melbourne, Flemington Road, Parkville, 3010, Australia.
³ Biodiversity and Geosciences, Queensland Museum, Grey Street, Brisbane, 4101, Australia.

Abstract

In order to further expand the NatureBank open access compound library, chemical investigations of the Australian marine sponge, Ianthella basta, were undertaken since UHPLC-MS analysis of the extract from this sponge indicated the presence of a new alkaloid. Large-scale extraction and mass-directed isolation studies on the CH₂Cl₂/MeOH I. basta extract resulted in the purification of a new bromotyrosine-derived alkaloid, 5-debromopurealidin H (1), along with the known marine natural product, ianthesine E (2). The chemical structure of the new compound was determined following detailed spectroscopic and spectrometric data analysis. These two compounds (1 and 2) along with seven previously reported marine bromotyrosine alkaloids from the NatureBank open access library, which included psammaplysins F (3) and H (4), bastadins 4 (5), 8 (6) and 13 (7), aerothionin (8) and hexadellin A (9), were evaluated for their nematocidal activity against exsheathed third-stage larvae of Haemonchus contortus, a highly pathogenic parasite of ruminants. Of the nine compounds, bastadin 8 (6), hexadellin A (9) and bastadin 4 (5) showed inhibition towards larval motility after 72 h of exposure with IC₅₀ values of 1.6 µM, 10.0 µM and 33.3 µM, respectively.

Keywords: 5-debromopurealidin H; Ianthella; NatureBank; alkaloid; anthelmintic; biodiscovery; bromotyrosine; sponge.

Grants and funding

The authors acknowledge the Australian Research Council (ARC) for support towards NMR and MS equipment (grants LE0668477, LE140100119, and LE0237908). Research at The University of Melbourne was supported by the ARC and Yourgene Health Singapore (LP180101085). S.H. acknowledges the Griffith Institute for Drug Discovery (Griffith University) for scholarship support.